JAX
Mouse Strain Datasheet - 004130
B6.129P2-Il18tm1Aki/J
Also Known As: Il18-
Il18-deficient mice exhibit reduced levels of interferon gamma in response to bacterial and lipopolysaccharide challenge, diminished natural killer cell activity, and impaired T helper lymphocyte response. These mice can be used to study the role of Il18 in inflammatory disorders.
Donating Investigator
Shizuo Akira, Osaka University
Genetic overview
| Genetic Background | Generation |
|---|---|
|
N11F11
(03-JUL-13) |
Il18tm1Aki
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Il18 | interleukin 18 |
Research Applications
- Immunology, Inflammation and Autoimmunity Research
- Research Tools
Detailed Description
Mice that are homozygous null for the Il18 gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Il18 gene product (mRNA or protein) is detected. Homozygous null mice exhibit reduced levels of interferon gamma in response to heat killed bacteria and lipopolysaccharide. IL-12 levels in the serum are similar to wild type after LPS challenge, indicating that the decreased interferon gamma response in Il18 deficient mice is not due to low induction of IL-12. Il18 deficient mice also exhibit diminished natural killer cell activity and impaired T helper lymphocyte response.
Development
A targeting vector containing neomycin resistance and Herpes simplex virus thymidine kinase genes was used to disrupt exons 3-5. The construct was transfected into 129P2/OlaHsd-derived E14-1 embryonic stem cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.
Control Suggestions
Selected References
- Takeda K; Tsutsui H; Yoshimoto T; Adachi O; Yoshida N; Kishimoto T ; Okamura H ; Nakanishi K ; Akira S. 1998. Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 8(3):383-90. PubMed: 9529155MGI: J:46514
Il18tm1Aki
Allele Symbol: Il18tm1Aki
| Allele Name | targeted mutation 1, Shizuo Akira |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | IL-18; IL-18-; Il18- |
| Gene Symbol and Name | Il18, interleukin 18 |
| Gene Synonym(s) | IGIF; IL-18; IL-1g; IL1F4; Igif; Igif; Il-18; interferon gamma inducing factor |
| Strain of Origin | 129P2/OlaHsd |
| Chromosome | 9 |
| Molecular Note | Replacement of exons 3, 4 and 5 with a neomycin resistance gene inserted in frame into exon 3. By Northern blot analysis, mRNA could not be detected in macrophages derived from homozygous mutant mice. By ELISA assay, protein cound not be detected in serum of homozygous mutant mice after intravenous injection of lipopolysaccharide. |
| Mutations Made By | Shizuo Akira, Osaka University |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
Genotype: Il18tm1Aki related
- Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- Immunodeficiency
- NK Cell Deficiency
- Inflammation
- Research Tools
- Immunology, Inflammation and Autoimmunity Research
- NK Cell Deficiency
- Immunology, Inflammation and Autoimmunity Research
Mammalian Phenotype Terms by Genotype
Genotype: Il18tm1Aki/Il18tm1Aki
B6.129P2-Il18tm1Aki
immune system phenotype
- impaired neutrophil chemotaxis
- less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae (MGI Ref ID J:125285)
- increased susceptibility to bacterial infection
- bacterial counts in the lung are 20-fold higher one day after infection with Haemophilus influenzae (MGI Ref ID J:125285)
- mice are able to clear infection from the lungs 10 days after infection, which is similar to wild-type mice (MGI Ref ID J:125285)
- there is less inflammation present in the lungs 6- and 24- hours after infection with histological scores significantly reduced compared to wild-type mice (MGI Ref ID J:125285)
- increased susceptibility to induced colitis
digestive/alimentary phenotype
- abnormal gut flora balance
- mice and co-housed wild-type mice exhibit expanded bacterial phylotypes compared with wild-type mice (MGI Ref ID J:173245)
- increased susceptibility to induced colitis
cellular phenotype
- impaired neutrophil chemotaxis
- less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae (MGI Ref ID J:125285)
hematopoietic system phenotype
- impaired neutrophil chemotaxis
- less numbers of neutrophils are recruited to the lung both 6- and 24 hours after infection with Haemophilus influenzae (MGI Ref ID J:125285)
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Il18tm1Aki/Il18+
involves: 129P2/OlaHsd
behavior/neurological phenotype
- polyphagia
- female mice overeat chow relative to wild-type mice during the last 6 hours of night and the first three hours in the day but not to the degree observed in Il18tm1Aki homozygotes (MGI Ref ID J:122588)
Genotype: Il18tm1Aki/Il18tm1Aki
involves: 129P2/OlaHsd
immune system phenotype
- abnormal T-helper 1 physiology
- abnormal macrophage physiology
- macrophages are resistant to cytotoxicity by SP1- Salmonella (MGI Ref ID J:112400)
- decreased circulating interferon-gamma level
- serum IFN-gamma levels are 1/5th of wild-type levels 6 hours after treatment with LPS in mice sensitized to Prionibacterium acnes (P. acnes) (MGI Ref ID J:46514)
- decreased circulating interleukin-18 level
- decreased interferon-gamma secretion
- splenic T cells produce about 1/10th the amount of IFN-gamma as T cells from wild-type mice 7 days after injection with heat killed P. acnes (MGI Ref ID J:46514)
- impaired natural killer cell mediated cytotoxicity
- normal level of target cell killing can be restored by in vivo administration of IL-18 for two days (MGI Ref ID J:46514)
- target cell killing can also be restored by in vivo pre-treatment with high amounts of IL-12 or the addition of small amounts of IL-12 to the co-culture (MGI Ref ID J:46514)
- the killing activity of splenic NK cells is about 1/3rd that of wild-type mice as measured by in vitro co-culturing with YAC-1 target cells (MGI Ref ID J:46514)
- increased susceptibility to bacterial infection
- mice succumb more rapidly than controls to 108 CFU of Salmonella with a median survival time of 6 days compared to 8 days for controls (MGI Ref ID J:112400)
- there is an average 30-fold-higher bacterial loads in infected Peyer's patches, mesenteric lymph nodes, and spleens than in the infected organs of wild-type animals (MGI Ref ID J:112400)
growth/size/body region phenotype
- increased susceptibility to age related obesity
- female mice have a greater body weight gain during the 5th month of life than controls going from 1% greater mean body weight at 4 months of age to 27% greater mean body weight at 5 months of age (MGI Ref ID J:122588)
- male mice have a 2-fold greater weight gain between 4 and 7 months of age with mean body weight being 14% higher by 27 weeks of age compared to controls (MGI Ref ID J:122588)
adipose tissue phenotype
- increased percent body fat/body weight
- weight gain is mostly due to increases in white fat resulting in a percent body fats that exceed 20% for mice 30 weeks in age (MGI Ref ID J:122588)
- increased total fat pad weight
- white fat pads are heavier on both absolute and relative scales with the largest increases occurring in the inguinal and gonadal pads where weights were 1 gram larger compared to controls (MGI Ref ID J:122588)
- increased white adipose tissue amount
- the collective white fat pad mass of these mice is 2-3 fold greater that of wild-type mice (MGI Ref ID J:122588)
homeostasis/metabolism phenotype
- decreased circulating interferon-gamma level
- serum IFN-gamma levels are 1/5th of wild-type levels 6 hours after treatment with LPS in mice sensitized to Prionibacterium acnes (P. acnes) (MGI Ref ID J:46514)
- decreased circulating interleukin-18 level
- decreased energy expenditure
- decreased oxygen consumption
behavior/neurological phenotype
- polyphagia
- during this period of the daily cycle mice will eat twice as much as controls (MGI Ref ID J:122588)
- hyperphagia also occurs on a low fat diet but not on a high fat diet when consumption is normalized to bodyweight (MGI Ref ID J:122588)
- hyperphagia is seen at 15 weeks of age before changes in body weight are observed (MGI Ref ID J:122588)
- hyperphagia varied according to the time of day with increase consumption occurring during the last six hours of the dark cycle and the first three hours of the light cycle (MGI Ref ID J:122588)
- overeating of chow increases later in adulthood for both female and male mice even when comsumption is normalized to bodyweight (MGI Ref ID J:122588)
hematopoietic system phenotype
- abnormal T-helper 1 physiology
- abnormal macrophage physiology
- macrophages are resistant to cytotoxicity by SP1- Salmonella (MGI Ref ID J:112400)
- impaired natural killer cell mediated cytotoxicity
- normal level of target cell killing can be restored by in vivo administration of IL-18 for two days (MGI Ref ID J:46514)
- target cell killing can also be restored by in vivo pre-treatment with high amounts of IL-12 or the addition of small amounts of IL-12 to the co-culture (MGI Ref ID J:46514)
- the killing activity of splenic NK cells is about 1/3rd that of wild-type mice as measured by in vitro co-culturing with YAC-1 target cells (MGI Ref ID J:46514)
Genotype: Il18tm1Aki/Il18tm1Aki
involves: 129P2/OlaHsd * C57BL/6
vision/eye phenotype
- abnormal retinal vasculature morphology
- abnormal blood vessels are found in the vitreous outside of the inner-limiting membrane in young mice (MGI Ref ID J:92254)
- mice 14 days of age have areas of the retina that are not perfused with capillaries (MGI Ref ID J:92254)
- mice 7 days of age display angiectasis and vascular leakage in the mid-periphery of the retina (MGI Ref ID J:92254)
- other blood vessels in the retina of young mice have a tortured appearance (MGI Ref ID J:92254)
- vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age (MGI Ref ID J:92254)
- retinal hemorrhage
cardiovascular system phenotype
- abnormal heart left ventricle morphology
- end diastolic volumes increased in response to pressure overload compared to wild-type mice that have decreased diastolic volumes (MGI Ref ID J:118183)
- hypertrophic growth of the left ventricle induced by pressure overload is significantly reduced compared to wild-type controls (MGI Ref ID J:118183)
- the left ventricular volume of 3-4 month old mice is reduced (MGI Ref ID J:118183)
- abnormal retinal vasculature morphology
- abnormal blood vessels are found in the vitreous outside of the inner-limiting membrane in young mice (MGI Ref ID J:92254)
- mice 14 days of age have areas of the retina that are not perfused with capillaries (MGI Ref ID J:92254)
- mice 7 days of age display angiectasis and vascular leakage in the mid-periphery of the retina (MGI Ref ID J:92254)
- other blood vessels in the retina of young mice have a tortured appearance (MGI Ref ID J:92254)
- vessel abnormalities lessen with age with the retina vasculature appearing normal by 84 days of age (MGI Ref ID J:92254)
- decreased ventricle muscle contractility
- left ventricle contractility decreased in response to pressure overload compared to the increases observed in wild-type mice (MGI Ref ID J:118183)
- retinal hemorrhage
hematopoietic system phenotype
- abnormal microglial cell morphology
- stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice (MGI Ref ID J:122031)
immune system phenotype
- abnormal microglial cell morphology
- stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice (MGI Ref ID J:122031)
nervous system phenotype
- abnormal microglial cell morphology
- stress-induced increase in microglial cell surface, which is a marker of activation, is significantly reduced by 1.5 to 3 fold in these mice (MGI Ref ID J:122031)
- decreased cerebral infarction size
- the neuropathological scores to measure brain injury resulting from HI were reduced with the most marked reduction of 35% occurring in the cerebral cortex (MGI Ref ID J:124249)
- the total volume of infarction caused by hypoxia-ischemia (HI) was reduced from 53% in wild-type mice to 42% in these mice (MGI Ref ID J:124249)
homeostasis/metabolism phenotype
- decreased cerebral infarction size
- the neuropathological scores to measure brain injury resulting from HI were reduced with the most marked reduction of 35% occurring in the cerebral cortex (MGI Ref ID J:124249)
- the total volume of infarction caused by hypoxia-ischemia (HI) was reduced from 53% in wild-type mice to 42% in these mice (MGI Ref ID J:124249)
muscle phenotype
- decreased ventricle muscle contractility
- left ventricle contractility decreased in response to pressure overload compared to the increases observed in wild-type mice (MGI Ref ID J:118183)
Genotype: Il18tm1Aki/Il18tm1Aki
C.129P2-Il18tm1Aki
digestive/alimentary phenotype
- gastrointestinal hemorrhage
- there is less bleeding associated with stress-induced ulcers in the stomach with bleeding index scores being about half that of wild-type mice (MGI Ref ID J:120594)
- hyperchlorhydria
- there is decreased secretion of gastric acid in the stomach 1- and 2- hours after stress induction compared to wild-type mice (MGI Ref ID J:120594)
- stomach inflammation
cardiovascular system phenotype
- gastrointestinal hemorrhage
- there is less bleeding associated with stress-induced ulcers in the stomach with bleeding index scores being about half that of wild-type mice (MGI Ref ID J:120594)
immune system phenotype
References
- Takeda K; Tsutsui H; Yoshimoto T; Adachi O; Yoshida N; Kishimoto T ; Okamura H ; Nakanishi K ; Akira S. 1998. Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 8(3):383-90. PubMed: 9529155MGI: J:46514
Additional - Il18tm1Aki related
- Aachoui Y; Leaf IA; Hagar JA; Fontana MF; Campos CG; Zak DE; Tan MH; Cotter PA; Vance RE; Aderem A; Miao EA. 2013. Caspase-11 protects against bacteria that escape the vacuole. Science 339(6122):975-8. PubMed: 23348507MGI: J:193387
- Adachi K; Tsutsui H; Kashiwamura S; Seki E; Nakano H; Takeuchi O; Takeda K; Okumura K; Van Kaer L; Okamura H; Akira S; Nakanishi K. 2001. Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. J Immunol 167(10):5928-34. PubMed: 11698470MGI: J:118004
- Akhiani AA; Schon K; Lycke N. 2004. Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice. J Immunol 173(5):3348-56. PubMed: 15322198MGI: J:92673
- Andoh T; Kishi H; Motoki K; Nakanishi K; Kuraishi Y; Muraguchi A. 2008. Protective effect of IL-18 on kainate- and IL-1beta-induced cerebellar ataxia in mice. J Immunol 180(4):2322-8. PubMed: 18250441MGI: J:131996
- Andoniou CE; van Dommelen SL; Voigt V; Andrews DM; Brizard G; Asselin-Paturel C; Delale T; Stacey KJ; Trinchieri G; Degli-Esposti MA. 2005. Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity. Nat Immunol 6(10):1011-9. PubMed: 16142239MGI: J:110194
- Ariga H; Shimohakamada Y; Nakada M; Tokunaga T; Kikuchi T; Kariyone A; Tamura T; Takatsu K. 2007. Instruction of naive CD4+ T-cell fate to T-bet expression and T helper 1 development: roles of T-cell receptor-mediated signals. Immunology 122(2):210-21. PubMed: 17490433MGI: J:125688
- Barquero-Calvo E; Chaves-Olarte E; Weiss DS; Guzman-Verri C; Chacon-Diaz C; Rucavado A; Moriyon I; Moreno E. 2007. Brucella abortus uses a stealthy strategy to avoid activation of the innate immune system during the onset of infection. PLoS One 2(7):e631. PubMed: 17637846MGI: J:129323
- Barr DP; Belz GT; Reading PC; Wojtasiak M; Whitney PG; Heath WR; Carbone FR; Brooks AG. 2007. A role for plasmacytoid dendritic cells in the rapid IL-18-dependent activation of NK cells following HSV-1 infection. Eur J Immunol 37(5):1334-42. PubMed: 17407097MGI: J:123560
- Bauer C; Kielian T; Wyatt TA; Romberger DJ; West WW; Gleason AM; Poole JA. 2013. Myeloid differentiation factor 88-dependent signaling is critical for acute organic dust-induced airway inflammation in mice. Am J Respir Cell Mol Biol 48(6):781-9. PubMed: 23492189MGI: J:211745
- Behera AK; Hildebrand E; Bronson RT; Perides G; Uematsu S; Akira S; Hu LT. 2006. MyD88 deficiency results in tissue-specific changes in cytokine induction and inflammation in interleukin-18-independent mice infected with Borrelia burgdorferi. Infect Immun 74(3):1462-70. PubMed: 16495516MGI: J:107422
- Birchenough GM; Nystrom EE; Johansson ME; Hansson GC. 2016. A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science 352(6293):1535-42. PubMed: 27339979MGI: J:233302
- Brigl M; Tatituri RV; Watts GF; Bhowruth V; Leadbetter EA; Barton N; Cohen NR; Hsu FF; Besra GS; Brenner MB. 2011. Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection. J Exp Med 208(6):1163-77. PubMed: 21555485MGI: J:177293
- Bruns DR; Buttrick PM; Walker LA. 2016. Genetic ablation of interleukin-18 does not attenuate hypobaric hypoxia-induced right ventricular hypertrophy. Am J Physiol Lung Cell Mol Physiol 310(6):L542-50. PubMed: 26747780MGI: J:232652
- Burt BM; Plitas G; Stableford JA; Nguyen HM; Bamboat ZM; Pillarisetty VG; DeMatteo RP. 2008. CD11c identifies a subset of murine liver natural killer cells that responds to adenoviral hepatitis. J Leukoc Biol 84(4):1039-46. PubMed: 18664530MGI: J:140218
- Cataisson C; Salcedo R; Hakim S; Moffitt BA; Wright L; Yi M; Stephens R; Dai RM; Lyakh L; Schenten D; Yuspa HS; Trinchieri G. 2012. IL-1R-MyD88 signaling in keratinocyte transformation and carcinogenesis. J Exp Med 209(9):1689-702. PubMed: 22908325MGI: J:191813
- Ceballos-Olvera I; Sahoo M; Miller MA; Del Barrio L; Re F. 2011. Inflammasome-dependent pyroptosis and IL-18 protect against Burkholderia pseudomallei lung infection while IL-1beta is deleterious. PLoS Pathog 7(12):e1002452. PubMed: 22241982MGI: J:183297
- Colston JT; Boylston WH; Feldman MD; Jenkinson CP; de la Rosa SD; Barton A; Trevino RJ; Freeman GL; Chandrasekar B. 2007. Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload. Biochem Biophys Res Commun 354(2):552-8. PubMed: 17250807MGI: J:118183
- Denton AE; Doherty PC; Turner SJ; La Gruta NL. 2007. IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8(+) T cells. Eur J Immunol 37(2):368-75. PubMed: 17219365MGI: J:117879
- Duan RS; Zhang XM; Mix E; Quezada HC; Adem A; Zhu J. 2007. IL-18 deficiency inhibits both Th1 and Th2 cytokine production but not the clinical symptoms in experimental autoimmune neuritis. J Neuroimmunol 183(1-2):162-7. PubMed: 17218016MGI: J:124505
- Dupaul-Chicoine J; Arabzadeh A; Dagenais M; Douglas T; Champagne C; Morizot A; Rodrigue-Gervais IG; Breton V; Colpitts SL; Beauchemin N; Saleh M. 2015. The Nlrp3 Inflammasome Suppresses Colorectal Cancer Metastatic Growth in the Liver by Promoting Natural Killer Cell Tumoricidal Activity. Immunity 43(4):751-63. PubMed: 26384545MGI: J:233785
- Elhage R; Jawien J; Rudling M; Ljunggren HG; Takeda K; Akira S; Bayard F; Hansson GK. 2003. Reduced atherosclerosis in interleukin-18 deficient apolipoprotein E-knockout mice. Cardiovasc Res 59(1):234-40. PubMed: 12829194MGI: J:102800
- Elinav E; Strowig T; Kau AL; Henao-Mejia J; Thaiss CA; Booth CJ; Peaper DR; Bertin J; Eisenbarth SC; Gordon JI; Flavell RA. 2011. NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis. Cell 145(5):745-57. PubMed: 21565393MGI: J:173245
- Eltom S; Belvisi MG; Stevenson CS; Maher SA; Dubuis E; Fitzgerald KA; Birrell MA. 2014. Role of the inflammasome-caspase1/11-IL-1/18 axis in cigarette smoke driven airway inflammation: an insight into the pathogenesis of COPD. PLoS One 9(11):e112829. PubMed: 25405768MGI: J:225298
- Gomes MT; Campos PC; Oliveira FS; Corsetti PP; Bortoluci KR; Cunha LD; Zamboni DS; Oliveira SC. 2013. Critical Role of ASC Inflammasomes and Bacterial Type IV Secretion System in Caspase-1 Activation and Host Innate Resistance to Brucella abortus Infection. J Immunol 190(7):3629-38. PubMed: 23460746MGI: J:194921
- Gosmann C; Frazer IH; Mattarollo SR; Blumenthal A. 2014. IL-18, but Not IL-12, Induces Production of IFN-gamma in the Immunosuppressive Environment of HPV16 E7 Transgenic Hyperplastic Skin. J Invest Dermatol 134(10):2562-9. PubMed: 24756108MGI: J:214254
- Gris D; Ye Z; Iocca HA; Wen H; Craven RR; Gris P; Huang M; Schneider M; Miller SD; Ting JP. 2010. NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J Immunol 185(2):974-81. PubMed: 20574004MGI: J:162018
- Guay HM; Andreyeva TA; Garcea RL; Welsh RM; Szomolanyi-Tsuda E. 2007. MyD88 is required for the formation of long-term humoral immunity to virus infection. J Immunol 178(8):5124-31. PubMed: 17404295MGI: J:145278
- Gutcher I; Urich E; Wolter K; Prinz M; Becher B. 2006. Interleukin 18-independent engagement of interleukin 18 receptor-alpha is required for autoimmune inflammation. Nat Immunol 7(9):946-53. PubMed: 16906165MGI: J:112650
- Haddad EA; Senger LK; Takei F. 2009. An accessory role for B cells in the IL-12-induced activation of resting mouse NK cells. J Immunol 183(6):3608-15. PubMed: 19710462MGI: J:152301
- Halpern MD; Khailova L; Molla-Hosseini D; Arganbright K; Reynolds C; Yajima M; Hoshiba J; Dvorak B. 2008. Decreased development of necrotizing enterocolitis in IL-18-deficient mice. Am J Physiol Gastrointest Liver Physiol 294(1):G20-6. PubMed: 17947451MGI: J:130516
- Hanada T; Date Y; Shimbara T; Sakihara S; Murakami N; Hayashi Y; Kanai Y; Suda T; Kangawa K; Nakazato M. 2003. Central actions of neuromedin U via corticotropin-releasing hormone. Biochem Biophys Res Commun 311(4):954-8. PubMed: 14623274MGI: J:113584
- Haring JS; Harty JT. 2009. Interleukin-18-related genes are induced during the contraction phase but do not play major roles in regulating the dynamics or function of the T-cell response to Listeria monocytogenes infection. Infect Immun 77(5):1894-903. PubMed: 19223481MGI: J:148206
- Hayashi N; Yoshimoto T; Izuhara K; Matsui K; Tanaka T; Nakanishi K. 2007. T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-{gamma} and IL-13 production. Proc Natl Acad Sci U S A 104(37):14765-70. PubMed: 17766435MGI: J:124973
- He Z; Dursun B; Oh DJ; Lu L; Faubel S; Edelstein CL. 2009. Macrophages are not the source of injurious interleukin-18 in ischemic acute kidney injury in mice. Am J Physiol Renal Physiol 296(3):F535-42. PubMed: 19129255MGI: J:145703
- Hedtjarn M; Leverin AL; Eriksson K; Blomgren K; Mallard C; Hagberg H. 2002. Interleukin-18 involvement in hypoxic-ischemic brain injury. J Neurosci 22(14):5910-9. PubMed: 12122053MGI: J:124249
- Hedtjarn M; Mallard C; Arvidsson P; Hagberg H. 2005. White matter injury in the immature brain: role of interleukin-18. Neurosci Lett 373(1):16-20. PubMed: 15555769MGI: J:104826
- Hedtjarn M; Mallard C; Iwakura Y; Hagberg H. 2005. Combined deficiency of IL-1beta18, but not IL-1alphabeta, reduces susceptibility to hypoxia-ischemia in the immature brain. Dev Neurosci 27(2-4):143-8. PubMed: 16046848MGI: J:104898
- Helmby H; Grencis RK. 2002. IL-18 regulates intestinal mastocytosis and Th2 cytokine production independently of IFN-gamma during Trichinella spiralis infection. J Immunol 169(5):2553-60. PubMed: 12193725MGI: J:120688
- Henao-Mejia J; Elinav E; Jin C; Hao L; Mehal WZ; Strowig T; Thaiss CA; Kau AL; Eisenbarth SC; Jurczak MJ; Camporez JP; Shulman GI; Gordon JI; Hoffman HM; Flavell RA. 2012. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384):179-85. PubMed: 22297845MGI: J:181354
- Hirano Y; Yasuma T; Mizutani T; Fowler BJ; Tarallo V; Yasuma R; Kim Y; Bastos-Carvalho A; Kerur N; Gelfand BD; Bogdanovich S; He S; Zhang X; Nozaki M; Ijima R; Kaneko H; Ogura Y; Terasaki H; Nagai H; Haro I; Nunez G; Ambati BK; Hinton DR; Ambati J. 2014. IL-18 is not therapeutic for neovascular age-related macular degeneration. Nat Med 20(12):1372-5. PubMed: 25473914MGI: J:227950
- Hu B; Elinav E; Huber S; Strowig T; Hao L; Hafemann A; Jin C; Eisenbarth SC; Flavell RA. 2013. Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc Natl Acad Sci U S A 110(24):9862-7. PubMed: 23696660MGI: J:197406
- Hu B; Jin C; Li HB; Tong J; Ouyang X; Cetinbas NM; Zhu S; Strowig T; Lam FC; Zhao C; Henao-Mejia J; Yilmaz O; Fitzgerald KA; Eisenbarth SC; Elinav E; Flavell RA. 2016. The DNA-sensing AIM2 inflammasome controls radiation-induced cell death and tissue injury. Science 354(6313):765-768. PubMed: 27846608MGI: J:236847
- Huang H; Chen HW; Evankovich J; Yan W; Rosborough BR; Nace GW; Ding Q; Loughran P; Beer-Stolz D; Billiar TR; Esmon CT; Tsung A. 2013. Histones activate the NLRP3 inflammasome in Kupffer cells during sterile inflammatory liver injury. J Immunol 191(5):2665-79. PubMed: 23904166MGI: J:205815
- Huber S; Gagliani N; Zenewicz LA; Huber FJ; Bosurgi L; Hu B; Hedl M; Zhang W; O'Connor W Jr; Murphy AJ; Valenzuela DM; Yancopoulos GD; Booth CJ; Cho JH; Ouyang W; Abraham C; Flavell RA. 2012. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491(7423):259-63. PubMed: 23075849MGI: J:189217
- Imaeda AB; Watanabe A; Sohail MA; Mahmood S; Mohamadnejad M; Sutterwala FS; Flavell RA; Mehal WZ. 2009. Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. J Clin Invest 119(2):305-14. PubMed: 19164858MGI: J:146148
- Inoue T; Aoyama-Ishikawa M; Kamoshida S; Nishino S; Sasano M; Oka N; Yamashita H; Kai M; Nakao A; Kotani J; Usami M. 2015. Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia. Reproduction 150(2):105-14. PubMed: 25934945MGI: J:226374
- Ishii KJ; Ito S; Tamura T; Hemmi H; Conover J; Ozato K; Akira S; Klinman DM. 2005. CpG-activated Thy1.2+ dendritic cells protect against lethal Listeria monocytogenes infection. Eur J Immunol 35(8):2397-405. PubMed: 16047338MGI: J:100431
- Iwai Y; Hemmi H; Mizenina O; Kuroda S; Suda K; Steinman RM. 2008. An IFN-gamma-IL-18 signaling loop accelerates memory CD8+ T cell proliferation. PLoS One 3(6):e2404. PubMed: 18545704MGI: J:137144
- Jha S; Srivastava SY; Brickey WJ; Iocca H; Toews A; Morrison JP; Chen VS; Gris D; Matsushima GK; Ting JP. 2010. The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J Neurosci 30(47):15811-20. PubMed: 21106820MGI: J:166978
- Joosten LA; Koenders MI; Smeets RL; Heuvelmans-Jacobs M; Helsen MM; Takeda K; Akira S; Lubberts E; van de Loo FA; van den Berg WB. 2003. Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation: critical role of myeloid differentiation factor 88. J Immunol 171(11):6145-53. PubMed: 14634130MGI: J:119063
- Kang SJ; Liang HE; Reizis B; Locksley RM. 2008. Regulation of hierarchical clustering and activation of innate immune cells by dendritic cells. Immunity 29(5):819-33. PubMed: 19006696MGI: J:142395
- Kastenmuller W; Torabi-Parizi P; Subramanian N; Lammermann T; Germain RN. 2012. A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread. Cell 150(6):1235-48. PubMed: 22980983MGI: J:187962
- Kawai T; Adachi O; Ogawa T; Takeda K; Akira S. 1999. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11(1):115-22. PubMed: 10435584MGI: J:91224
- Kawakami K; Kinjo Y; Uezu K; Miyagi K; Kinjo T; Yara S; Koguchi Y; Miyazato A; Shibuya K; Iwakura Y; Takeda K; Akira S; Saito A. 2004. Interferon-gamma production and host protective response against Mycobacterium tuberculosis in mice lacking both IL-12p40 and IL-18. Microbes Infect 6(4):339-49. PubMed: 15050961MGI: J:105389
- Kawakami K; Kinjo Y; Yara S; Uezu K; Koguchi Y; Tohyama M; Azuma M; Takeda K; Akira S; Saito A. 2001. Enhanced Gamma Interferon Production through Activation of Valpha14(+) Natural Killer T Cells by alpha-Galactosylceramide in Interleukin-18-Deficient Mice with Systemic Cryptococcosis. Infect Immun 69(11):6643-50. PubMed: 11598033MGI: J:72191
- Kawakami K; Koguchi Y; Qureshi MH; Miyazato A; Yara S; Kinjo Y; Iwakura Y; Takeda K; Akira S; Kurimoto M; Saito A. 2000. IL-18 contributes to host resistance against infection with Cryptococcus neoformans in mice with defective IL-12 synthesis through induction of IFN-gamma production by NK cells. J Immunol 165(2):941-7. PubMed: 10878369MGI: J:120529
- Kawane K; Tanaka H; Kitahara Y; Shimaoka S; Nagata S. 2010. Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation. Proc Natl Acad Sci U S A 107(45):19432-7. PubMed: 20974942MGI: J:167378
- Kim ML; Chae JJ; Park YH; De Nardo D; Stirzaker RA; Ko HJ; Tye H; Cengia L; DiRago L; Metcalf D; Roberts AW; Kastner DL; Lew AM; Lyras D; Kile BT; Croker BA; Masters SL. 2015. Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1beta. J Exp Med 212(6):927-38. PubMed: 26008898MGI: J:224778
- Kinjo Y; Kawakami K; Uezu K; Yara S; Miyagi K; Koguchi Y; Hoshino T; Okamoto M; Kawase Y; Yokota K; Yoshino K; Takeda K; Akira S; Saito A. 2002. Contribution of IL-18 to Th1 response and host defense against infection by Mycobacterium tuberculosis: a comparative study with IL-12p40. J Immunol 169(1):323-9. PubMed: 12077261MGI: J:123789
- Kitching AR; Turner AL; Wilson GR; Semple T; Odobasic D; Timoshanko JR; O'Sullivan KM; Tipping PG; Takeda K; Akira S; Holdsworth SR. 2005. IL-12p40 and IL-18 in crescentic glomerulonephritis: IL-12p40 is the key Th1-defining cytokine chain, whereas IL-18 promotes local inflammation and leukocyte recruitment. J Am Soc Nephrol 16(7):2023-33. PubMed: 15888563MGI: J:114369
- Konishi H; Tsutsui H; Murakami T; Yumikura-Futatsugi S; Yamanaka K; Tanaka M; Iwakura Y; Suzuki N; Takeda K; Akira S; Nakanishi K; Mizutani H. 2002. IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions. Proc Natl Acad Sci U S A 99(17):11340-5. PubMed: 12151598MGI: J:78602
- Kordes M; Matuschewski K; Hafalla JC. 2011. Caspase-1 Activation of Interleukin-1{beta} (IL-1{beta}) and IL-18 Is Dispensable for Induction of Experimental Cerebral Malaria. Infect Immun 79(9):3633-41. PubMed: 21708993MGI: J:175707
- Krebs P; Barnes MJ; Lampe K; Whitley K; Bahjat KS; Beutler B; Janssen E; Hoebe K. 2009. NK cell-mediated killing of target cells triggers robust antigen-specific T cell-mediated and humoral responses. Blood 113(26):6593-602. PubMed: 19406986MGI: J:150150
- Kupz A; Guarda G; Gebhardt T; Sander LE; Short KR; Diavatopoulos DA; Wijburg OL; Cao H; Waithman JC; Chen W; Fernandez-Ruiz D; Whitney PG; Heath WR; Curtiss R 3rd; Tschopp J; Strugnell RA; Bedoui S. 2012. NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8 T cells. Nat Immunol 13(2):162-9. PubMed: 22231517MGI: J:181212
- Lamkanfi M; Sarkar A; Vande Walle L; Vitari AC; Amer AO; Wewers MD; Tracey KJ; Kanneganti TD; Dixit VM. 2010. Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia. J Immunol 185(7):4385-92. PubMed: 20802146MGI: J:164216
- Lebeis SL; Powell KR; Merlin D; Sherman MA; Kalman D. 2009. Interleukin-1 receptor signaling protects mice from lethal intestinal damage caused by the attaching and effacing pathogen Citrobacter rodentium. Infect Immun 77(2):604-14. PubMed: 19075023MGI: J:143737
- Levy M; Thaiss CA; Zeevi D; Dohnalova L; Zilberman-Schapira G; Mahdi JA; David E; Savidor A; Korem T; Herzig Y; Pevsner-Fischer M; Shapiro H; Christ A; Harmelin A; Halpern Z; Latz E; Flavell RA; Amit I; Segal E; Elinav E. 2015. Microbiota-Modulated Metabolites Shape the Intestinal Microenvironment by Regulating NLRP6 Inflammasome Signaling. Cell 163(6):1428-43. PubMed: 26638072MGI: J:227991
- Lewis EC; Dinarello CA. 2006. Responses of IL-18- and IL-18 receptor-deficient pancreatic islets with convergence of positive and negative signals for the IL-18 receptor. Proc Natl Acad Sci U S A 103(45):16852-7. PubMed: 17075045MGI: J:117139
- Li W; Jin D; Hata M; Takai S; Yamanishi K; Shen W; El-Darawish Y; Yamanishi H; Okamura H. 2016. Dysfunction of mitochondria and deformed gap junctions in the heart of IL-18-deficient mice. Am J Physiol Heart Circ Physiol 311(2):H313-25. PubMed: 27288439MGI: J:236263
- Li W; Kashiwamura S; Ueda H; Sekiyama A; Okamura H. 2007. Protection of CD8+ T cells from activation-induced cell death by IL-18. J Leukoc Biol 82(1):142-51. PubMed: 17400610MGI: J:122662
- Lichtnekert J; Kulkarni OP; Mulay SR; Rupanagudi KV; Ryu M; Allam R; Vielhauer V; Muruve D; Lindenmeyer MT; Cohen CD; Anders HJ. 2011. Anti-GBM Glomerulonephritis Involves IL-1 but Is Independent of NLRP3/ASC Inflammasome-Mediated Activation of Caspase-1. PLoS One 6(10):e26778. PubMed: 22046355MGI: J:178074
- Liu R; Van Kaer L; La Cava A; Price M; Campagnolo DI; Collins M; Young DA; Vollmer TL; Shi FD. 2006. Autoreactive T cells mediate NK cell degeneration in autoimmune disease. J Immunol 176(9):5247-54. PubMed: 16621990MGI: J:131629
- Liu Z; Zaki MH; Vogel P; Gurung P; Finlay BB; Deng W; Lamkanfi M; Kanneganti TD. 2012. Role of inflammasomes in host defense against Citrobacter rodentium infection. J Biol Chem 287(20):16955-64. PubMed: 22461621MGI: J:185438
- Mager LF; Riether C; Schurch CM; Banz Y; Wasmer MH; Stuber R; Theocharides AP; Li X; Xia Y; Saito H; Nakae S; Baerlocher GM; Manz MG; McCoy KD; Macpherson AJ; Ochsenbein AF; Beutler B; Krebs P. 2015. IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms. J Clin Invest 125(7):2579-91. PubMed: 26011644MGI: J:224475
- Marshall HD; Prince AL; Berg LJ; Welsh RM. 2010. IFN-alphabeta and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions. J Immunol 185(3):1419-28. PubMed: 20592282MGI: J:162457
- Masters SL; Gerlic M; Metcalf D; Preston S; Pellegrini M; O'Donnell JA; McArthur K; Baldwin TM; Chevrier S; Nowell CJ; Cengia LH; Henley KJ; Collinge JE; Kastner DL; Feigenbaum L; Hilton DJ; Alexander WS; Kile BT; Croker BA. 2012. NLRP1 Inflammasome Activation Induces Pyroptosis of Hematopoietic Progenitor Cells. Immunity 37(6):1009-23. PubMed: 23219391MGI: J:191055
- Mayer-Barber KD; Barber DL; Shenderov K; White SD; Wilson MS; Cheever A; Kugler D; Hieny S; Caspar P; Nunez G; Schlueter D; Flavell RA; Sutterwala FS; Sher A. 2010. Caspase-1 independent IL-1beta production is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo. J Immunol 184(7):3326-30. PubMed: 20200276MGI: J:160077
- Miao EA; Leaf IA; Treuting PM; Mao DP; Dors M; Sarkar A; Warren SE; Wewers MD; Aderem A. 2010. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol 11(12):1136-42. PubMed: 21057511MGI: J:167323
- Millward JM; Lobner M; Wheeler RD; Owens T. 2010. Inflammation in the central nervous system and Th17 responses are inhibited by IFN-gamma-Induced IL-18 binding protein. J Immunol 185(4):2458-66. PubMed: 20644165MGI: J:162621
- Mitchell AJ; Yau B; McQuillan JA; Ball HJ; Too LK; Abtin A; Hertzog P; Leib SL; Jones CA; Gerega SK; Weninger W; Hunt NH. 2012. Inflammasome-dependent IFN-gamma drives pathogenesis in Streptococcus pneumoniae meningitis. J Immunol 189(10):4970-80. PubMed: 23071286MGI: J:190696
- Mori I; Hossain MJ; Takeda K; Okamura H; Imai Y; Kohsaka S; Kimura Y. 2001. Impaired microglial activation in the brain of IL-18-gene-disrupted mice after neurovirulent influenza A virus infection. Virology 287(1):163-70. PubMed: 11504551MGI: J:71064
- Mulay SR; Kulkarni OP; Rupanagudi KV; Migliorini A; Darisipudi MN; Vilaysane A; Muruve D; Shi Y; Munro F; Liapis H; Anders HJ. 2013. Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1beta secretion. J Clin Invest 123(1):236-46. PubMed: 23221343MGI: J:194155
- Murphy AJ; Kraakman MJ; Kammoun HL; Dragoljevic D; Lee MK; Lawlor KE; Wentworth JM; Vasanthakumar A; Gerlic M; Whitehead LW; DiRago L; Cengia L; Lane RM; Metcalf D; Vince JE; Harrison LC; Kallies A; Kile BT; Croker BA; Febbraio MA; Masters SL. 2016. IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome. Cell Metab 23(1):155-64. PubMed: 26603191MGI: J:232742
- Murray HW; Tsai CW; Liu J; Ma X. 2006. Responses to Leishmania donovani in mice deficient in interleukin-12 (IL-12), IL-12/IL-23, or IL-18. Infect Immun 74(7):4370-4. PubMed: 16790814MGI: J:110039
- Nagarajan NA; Kronenberg M. 2007. Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J Immunol 178(5):2706-13. PubMed: 17312112MGI: J:144118
- Naik S; Bouladoux N; Wilhelm C; Molloy MJ; Salcedo R; Kastenmuller W; Deming C; Quinones M; Koo L; Conlan S; Spencer S; Hall JA; Dzutsev A; Kong H; Campbell DJ; Trinchieri G; Segre JA; Belkaid Y. 2012. Compartmentalized control of skin immunity by resident commensals. Science 337(6098):1115-9. PubMed: 22837383MGI: J:187389
- Nakae S; Suto H; Berry GJ; Galli SJ. 2007. Mast cell-derived TNF can promote Th17 cell-dependent neutrophil recruitment in ovalbumin-challenged OTII mice. Blood 109(9):3640-8. PubMed: 17197430MGI: J:145332
- Nakasone C; Kawakami K; Hoshino T; Kawase Y; Yokota K; Yoshino K; Takeda K; Akira S; Saito A. 2004. Limited role for interleukin-18 in the host protection response to pulmonary infection with Pseudomonas aeruginosa in mice. Infect Immun 72(10):6176-80. PubMed: 15385528MGI: J:93126
- Nakatani-Okuda A; Ueda H; Kashiwamura S; Sekiyama A; Kubota A; Fujita Y; Adachi S; Tsuji Y; Tanizawa T; Okamura H. 2005. Protection against bleomycin-induced lung injury by IL-18 in mice. Am J Physiol Lung Cell Mol Physiol 289(2):L280-7. PubMed: 15792964MGI: J:104755
- Netea MG; Joosten LA; Lewis E; Jensen DR; Voshol PJ; Kullberg BJ; Tack CJ; van Krieken H; Kim SH; Stalenhoef AF; van de Loo FA; Verschueren I; Pulawa L; Akira S; Eckel RH; Dinarello CA; van den Berg W; van der Meer JW. 2006. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat Med 12(6):650-656. PubMed: 16732281MGI: J:109552
- Nishida K; Kamizato M; Kawai T; Masuda K; Takeo K; Teshima-Kondo S; Tanahashi T; Rokutan K. 2009. Interleukin-18 is a crucial determinant of vulnerability of the mouse rectum to psychosocial stress. FASEB J 23(6):1797-805. PubMed: 19141531MGI: J:150555
- Obar JJ; Jellison ER; Sheridan BS; Blair DA; Pham QM; Zickovich JM; Lefrancois L. 2011. Pathogen-induced inflammatory environment controls effector and memory CD8+ T cell differentiation. J Immunol 187(10):4967-78. PubMed: 21987662MGI: J:179638
- Oosting M; van de Veerdonk FL; Kanneganti TD; Sturm P; Verschueren I; Berende A; van der Meer JW; Kullberg BJ; Netea MG; Joosten LA. 2011. Borrelia species induce inflammasome activation and IL-17 production through a caspase-1-dependent mechanism. Eur J Immunol 41(1):172-81. PubMed: 21182088MGI: J:174656
- Paget C; Chow MT; Duret H; Mattarollo SR; Smyth MJ. 2012. Role of gammadelta T cells in alpha-galactosylceramide-mediated immunity. J Immunol 188(8):3928-39. PubMed: 22412194MGI: J:184074
- Panthel K; Faller G; Haas R. 2003. Colonization of C57BL/6J and BALB/c wild-type and knockout mice with Helicobacter pylori: effect of vaccination and implications for innate and acquired immunity. Infect Immun 71(2):794-800. PubMed: 12540559MGI: J:81703
- Pedra JH; Sutterwala FS; Sukumaran B; Ogura Y; Qian F; Montgomery RR; Flavell RA; Fikrig E. 2007. ASC/PYCARD and caspase-1 regulate the IL-18/IFN-gamma axis during Anaplasma phagocytophilum infection. J Immunol 179(7):4783-91. PubMed: 17878377MGI: J:152337
- Pejnovic N; Vratimos A; Lee SH; Popadic D; Takeda K; Akira S; Chan WL. 2009. Increased atherosclerotic lesions and Th17 in interleukin-18 deficient apolipoprotein E-knockout mice fed high-fat diet. Mol Immunol 47(1):37-45. PubMed: 19201478MGI: J:155263
- Pien GC; Nguyen KB; Malmgaard L; Satoskar AR; Biron CA. 2002. A unique mechanism for innate cytokine promotion of T cell responses to viral infections. J Immunol 169(10):5827-37. PubMed: 12421964MGI: J:80075
- Pien GC; Satoskar AR; Takeda K; Akira S; Biron CA. 2000. Cutting edge: selective IL-18 requirements for induction of compartmental IFN-gamma responses during viral infection. J Immunol 165(9):4787-91. PubMed: 11046000MGI: J:119583
- Place DE; Muse SJ; Kirimanjeswara GS; Harvill ET. 2014. Caspase-1-independent interleukin-1beta is required for clearance of Bordetella pertussis infections and whole-cell vaccine-mediated immunity. PLoS One 9(9):e107188. PubMed: 25198773MGI: J:221522
- Price JD; Simpfendorfer KR; Mantena RR; Holden J; Heath WR; van Rooijen N; Strugnell RA; Wijburg OL. 2007. Gamma interferon-independent effects of interleukin-12 on immunity to Salmonella enterica serovar Typhimurium. Infect Immun 75(12):5753-62. PubMed: 17875635MGI: J:127653
- Qiao H; Sonoda KH; Ikeda Y; Yoshimura T; Hijioka K; Jo YJ; Sassa Y; Tsutsumi-Miyahara C; Hata Y; Akira S; Ishibashi T. 2007. Interleukin-18 regulates pathological intraocular neovascularization. J Leukoc Biol 81(4):1012-21. PubMed: 17234681MGI: J:121444
- Qiao H; Sonoda KH; Sassa Y; Hisatomi T; Yoshikawa H; Ikeda Y; Murata T; Akira S; Ishibashi T. 2004. Abnormal retinal vascular development in IL-18 knockout mice. Lab Invest 84(8):973-80. PubMed: 15122309MGI: J:92254
- Qiao S; Okret S; Jondal M. 2009. Thymocyte-synthesized glucocorticoids play a role in thymocyte homeostasis and are down-regulated by adrenocorticotropic hormone. Endocrinology 150(9):4163-9. PubMed: 19406942MGI: J:158152
- Raupach B; Peuschel SK; Monack DM; Zychlinsky A. 2006. Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infect Immun 74(8):4922-6. PubMed: 16861683MGI: J:112400
- Reading PC; Whitney PG; Barr DP; Wojtasiak M; Mintern JD; Waithman J; Brooks AG. 2007. IL-18, but not IL-12, regulates NK cell activity following intranasal herpes simplex virus type 1 infection. J Immunol 179(5):3214-21. PubMed: 17709537MGI: J:151826
- Santos LL; Milenkovski GP; Hall PH; Leech M; Sharma L; Takeda K; Akira S; Kitching AR; Morand EF. 2006. IL-18 is redundant in T-cell responses and in joint inflammation in antigen-induced arthritis. Immunol Cell Biol 84(2):166-73. PubMed: 16519734MGI: J:105836
- Sarkar A; Hall MW; Exline M; Hart J; Knatz N; Gatson NT; Wewers MD. 2006. Caspase-1 regulates Escherichia coli sepsis and splenic B cell apoptosis independently of interleukin-1beta and interleukin-18. Am J Respir Crit Care Med 174(9):1003-10. PubMed: 16908867MGI: J:135846
- Sasaki Y; Yoshimoto T; Maruyama H; Tegoshi T; Ohta N; Arizono N; Nakanishi K. 2005. IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity. J Exp Med 202(5):607-16. PubMed: 16129701MGI: J:100697
- Sawaki J; Tsutsui H; Hayashi N; Yasuda K; Akira S; Tanizawa T; Nakanishi K. 2007. Type 1 cytokine/chemokine production by mouse NK cells following activation of their TLR/MyD88-mediated pathways. Int Immunol 19(3):311-20. PubMed: 17289654MGI: J:118680
- Schieber AM; Lee YM; Chang MW; Leblanc M; Collins B; Downes M; Evans RM; Ayres JS. 2015. Disease tolerance mediated by microbiome E. coli involves inflammasome and IGF-1 signaling. Science 350(6260):558-63. PubMed: 26516283MGI: J:226609
- Schneider BE; Korbel D; Hagens K; Koch M; Raupach B; Enders J; Kaufmann SH; Mittrucker HW; Schaible UE. 2010. A role for IL-18 in protective immunity against Mycobacterium tuberculosis. Eur J Immunol 40(2):396-405. PubMed: 19950174MGI: J:157785
- Seino H; Ueda H; Kokai M; Tsuji NM; Kashiwamura S; Morita Y; Okamura H. 2007. IL-18 mediates the formation of stress-induced, histamine-dependent gastric lesions. Am J Physiol Gastrointest Liver Physiol 292(1):G262-7. PubMed: 16959946MGI: J:120594
- Seki E; Tsutsui H; Tsuji NM; Hayashi N; Adachi K; Nakano H; Futatsugi-Yumikura S; Takeuchi O; Hoshino K; Akira S; Fujimoto J; Nakanishi K. 2002. Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. J Immunol 169(7):3863-8. PubMed: 12244183MGI: J:120385
- Sekiyama A; Ueda H; Kashiwamura SI; Sekiyama R; Takeda M; Rokutan K; Okamura H. 2005. A Stress-Induced, Superoxide-Mediated Caspase-1 Activation Pathway Causes Plasma IL-18 Upregulation. Immunity 22(6):669-677. PubMed: 15963782MGI: J:99113
- Shaw PJ; Ditewig AC; Waring JF; Liguori MJ; Blomme EA; Ganey PE; Roth RA. 2009. Coexposure of mice to trovafloxacin and lipopolysaccharide, a model of idiosyncratic hepatotoxicity, results in a unique gene expression profile and interferon gamma-dependent liver injury. Toxicol Sci 107(1):270-80. PubMed: 18930950MGI: J:144560
- Shi FD; Takeda K; Akira S; Sarvetnick N; Ljunggren HG. 2000. IL-18 directs autoreactive T cells and promotes autodestruction in the central nervous system via induction of IFN-gamma by NK cells. J Immunol 165(6):3099-104. PubMed: 10975822MGI: J:64550
- Shi FD; Wang HB; Li H; Hong S; Taniguchi M; Link H; Van Kaer L; Ljunggren HG. 2000. Natural killer cells determine the outcome of B cell-mediated autoimmunity. Nat Immunol 1(3):245-51. PubMed: 10973283MGI: J:64350
- Shigeoka AA; Mueller JL; Kambo A; Mathison JC; King AJ; Hall WF; Correia Jda S; Ulevitch RJ; Hoffman HM; McKay DB. 2010. An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury. J Immunol 185(10):6277-85. PubMed: 20962258MGI: J:166055
- Singh N; Gurav A; Sivaprakasam S; Brady E; Padia R; Shi H; Thangaraju M; Prasad PD; Manicassamy S; Munn DH; Lee JR; Offermanns S; Ganapathy V. 2014. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40(1):128-39. PubMed: 24412617MGI: J:209390
- Smyth MJ; Wallace ME; Nutt SL; Yagita H; Godfrey DI; Hayakawa Y. 2005. Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer. J Exp Med 201(12):1973-85. PubMed: 15967825MGI: J:99284
- Srinivasan A; Salazar-Gonzalez RM; Jarcho M; Sandau MM; Lefrancois L; McSorley SJ. 2007. Innate immune activation of CD4 T cells in salmonella-infected mice is dependent on IL-18. J Immunol 178(10):6342-9. PubMed: 17475863MGI: J:146116
- Street SE; Trapani JA; MacGregor D; Smyth MJ. 2002. Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J Exp Med 196(1):129-34. PubMed: 12093877MGI: J:77491
- Sugama S; Fujita M; Hashimoto M; Conti B. 2007. Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18. Neuroscience 146(3):1388-99. PubMed: 17433555MGI: J:122031
- Sugama S; Wirz SA; Barr AM; Conti B; Bartfai T; Shibasaki T. 2004. Interleukin-18 null mice show diminished microglial activation and reduced dopaminergic neuron loss following acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. Neuroscience 128(2):451-8. PubMed: 15350655MGI: J:93613
- Swann JB; Vesely MD; Silva A; Sharkey J; Akira S; Schreiber RD; Smyth MJ. 2008. Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis. Proc Natl Acad Sci U S A 105(2):652-6. PubMed: 18178624MGI: J:131026
- Takeda K; Cretney E; Hayakawa Y; Ota T; Akiba H; Ogasawara K; Yagita H; Kinoshita K; Okumura K; Smyth MJ. 2005. TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. Blood 105(5):2082-9. PubMed: 15536146MGI: J:98142
- Takeda K; Nakayama M; Sakaki M; Hayakawa Y; Imawari M; Ogasawara K; Okumura K; Smyth MJ. 2011. IFN-gamma production by lung NK cells is critical for the natural resistance to pulmonary metastasis of B16 melanoma in mice. J Leukoc Biol 90(4):777-85. PubMed: 21712396MGI: J:177544
- Terada M; Tsutsui H; Imai Y; Yasuda K; Mizutani H; Yamanishi K; Kubo M; Matsui K; Sano H; Nakanishi K. 2006. Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. Proc Natl Acad Sci U S A 103(23):8816-21. PubMed: 16723395MGI: J:110807
- Toldo S; Mezzaroma E; O'Brien L; Marchetti C; Seropian IM; Voelkel NF; Van Tassell BW; Dinarello CA; Abbate A. 2014. Interleukin-18 mediates interleukin-1-induced cardiac dysfunction. Am J Physiol Heart Circ Physiol 306(7):H1025-31. PubMed: 24531812MGI: J:210478
- Trunk G; Oxenius A. 2012. Innate instruction of CD4+ T cell immunity in respiratory bacterial infection. J Immunol 189(2):616-28. PubMed: 22723524MGI: J:189793
- Tsutsui H; Kayagaki N; Kuida K; Nakano H; Hayashi N; Takeda K; Matsui K; Kashiwamura S; Hada T; Akira S; Yagita H; Okamura H; Nakanishi K. 1999. Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice. Immunity 11(3):359-67. PubMed: 10514014MGI: J:57879
- Tyznik AJ; Tupin E; Nagarajan NA; Her MJ; Benedict CA; Kronenberg M. 2008. Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals. J Immunol 181(7):4452-6. PubMed: 18802047MGI: J:141301
- Tyznik AJ; Verma S; Wang Q; Kronenberg M; Benedict CA. 2014. Distinct requirements for activation of NKT and NK cells during viral infection. J Immunol 192(8):3676-85. PubMed: 24634489MGI: J:210013
- Ulland TK; Janowski AM; Buchan BW; Faron M; Cassel SL; Jones BD; Sutterwala FS. 2013. Francisella tularensis Live Vaccine Strain Folate Metabolism and Pseudouridine Synthase Gene Mutants Modulate Macrophage Caspase-1 Activation. Infect Immun 81(1):201-8. PubMed: 23115038MGI: J:190664
- Van Der Sluijs KF; Van Elden LJ; Arens R; Nijhuis M; Schuurman R; Florquin S; Kwakkel J; Akira S; Jansen HM; Lutter R; Van Der Polls T. 2005. Enhanced viral clearance in interleukin-18 gene-deficient mice after pulmonary infection with influenza A virus. Immunology 114(1):112-20. PubMed: 15606801MGI: J:94687
- Vladimer GI; Weng D; Paquette SW; Vanaja SK; Rathinam VA; Aune MH; Conlon JE; Burbage JJ; Proulx MK; Liu Q; Reed G; Mecsas JC; Iwakura Y; Bertin J; Goguen JD; Fitzgerald KA; Lien E. 2012. The NLRP12 inflammasome recognizes Yersinia pestis. Immunity 37(1):96-107. PubMed: 22840842MGI: J:187388
- Vossenkamper A; Struck D; Alvarado-Esquivel C; Went T; Takeda K; Akira S; Pfeffer K; Alber G; Lochner M; Forster I; Liesenfeld O. 2004. Both IL-12 and IL-18 contribute to small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii, but IL-12 is dominant over IL-18 in parasite control. Eur J Immunol 34(11):3197-207. PubMed: 15368276MGI: J:93844
- Wang X; Hagberg H; Mallard C; Zhu C; Hedtjarn M; Tiger CF; Eriksson K; Rosen A; Jacobsson B. 2006. Disruption of interleukin-18, but not interleukin-1, increases vulnerability to preterm delivery and fetal mortality after intrauterine inflammation. Am J Pathol 169(3):967-76. PubMed: 16936270MGI: J:112345
- Wang Y; Chaudhri G; Jackson RJ; Karupiah G. 2009. IL-12p40 and IL-18 play pivotal roles in orchestrating the cell-mediated immune response to a poxvirus infection. J Immunol 183(5):3324-31. PubMed: 19657092MGI: J:151861
- Weiss DS; Takeda K; Akira S; Zychlinsky A; Moreno E. 2005. MyD88, but not toll-like receptors 4 and 2, is required for efficient clearance of Brucella abortus. Infect Immun 73(8):5137-43. PubMed: 16041030MGI: J:100421
- Wheeler RD; Brough D; Le Feuvre RA; Takeda K; Iwakura Y; Luheshi GN; Rothwell NJ. 2003. Interleukin-18 induces expression and release of cytokines from murine glial cells: interactions with interleukin-1 beta. J Neurochem 85(6):1412-20. PubMed: 12787061MGI: J:126730
- Wieland CW; Florquin S; Pater JM; Weijer S; van der Poll T. 2006. CD4+ cells play a limited role in murine lung infection with Mycobacterium kansasii. Am J Respir Cell Mol Biol 34(2):167-73. PubMed: 16195537MGI: J:120194
- Wieland CW; Florquin S; van der Poll T. 2007. Interleukin 18 participates in the early inflammatory response and bacterial clearance during pneumonia caused by nontypeable Haemophilus influenzae. Infect Immun 75(10):5068-72. PubMed: 17664259MGI: J:125285
- Wlodarska M; Thaiss CA; Nowarski R; Henao-Mejia J; Zhang JP; Brown EM; Frankel G; Levy M; Katz MN; Philbrick WM; Elinav E; Finlay BB; Flavell RA. 2014. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156(5):1045-59. PubMed: 24581500MGI: J:212020
- Wolf G; Yirmiya R; Goshen I; Iverfeldt K; Holmlund L; Takeda K; Shavit Y. 2003. Impairment of interleukin-1 (IL-1) signaling reduces basal pain sensitivity in mice: genetic, pharmacological and developmental aspects. Pain 104(3):471-80. PubMed: 12927619MGI: J:118738
- Wyburn K; Wu H; Chen G; Yin J; Eris J; Chadban S. 2006. Interleukin-18 affects local cytokine expression but does not impact on the development of kidney allograft rejection. Am J Transplant 6(11):2612-21. PubMed: 17049054MGI: J:135970
- Yamagata S; Tomita K; Sato R; Niwa A; Higashino H; Tohda Y. 2008. Interleukin-18-deficient mice exhibit diminished chronic inflammation and airway remodelling in ovalbumin-induced asthma model. Clin Exp Immunol 154(3):295-304. PubMed: 18826499MGI: J:142814
- Zanoni I; Spreafico R; Bodio C; Di Gioia M; Cigni C; Broggi A; Gorletta T; Caccia M; Chirico G; Sironi L; Collini M; Colombo MP; Garbi N; Granucci F. 2013. IL-15 cis presentation is required for optimal NK cell activation in lipopolysaccharide-mediated inflammatory conditions. Cell Rep 4(6):1235-49. PubMed: 24055061MGI: J:203792
- Zhang JH; He H; Borzychowski AM; Takeda K; Akira S; Croy BA. 2003. Analysis of cytokine regulators inducing interferon production by mouse uterine natural killer cells. Biol Reprod 69(2):404-11. PubMed: 12646495MGI: J:84561
- Zhang XM; Duan RS; Chen Z; Quezada HC; Mix E; Winblad B; Zhu J. 2007. IL-18 deficiency aggravates kainic acid-induced hippocampal neurodegeneration in C57BL/6 mice due to an overcompensation by IL-12. Exp Neurol 205(1):64-73. PubMed: 17316614MGI: J:141588
- Zhou S; Kurt-Jones EA; Cerny AM; Chan M; Bronson RT; Finberg RW. 2009. MyD88 intrinsically regulates CD4 T-cell responses. J Virol 83(4):1625-34. PubMed: 19052080MGI: J:153385
- Zorrilla EP; Sanchez-Alavez M; Sugama S; Brennan M; Fernandez R; Bartfai T; Conti B. 2007. Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency. Proc Natl Acad Sci U S A 104(26):11097-102. PubMed: 17578927MGI: J:122588
- Zwijnenburg PJ; van der Poll T; Florquin S; Akira S; Takeda K; Roord JJ; van Furth AM. 2003. Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis. J Neuroimmunol 138(1-2):31-7. PubMed: 12742650MGI: J:119043
- van de Veerdonk FL; Joosten LA; Shaw PJ; Smeekens SP; Malireddi RK; van der Meer JW; Kullberg BJ; Netea MG; Kanneganti TD. 2011. The inflammasome drives protective Th1 and Th17 cellular responses in disseminated candidiasis. Eur J Immunol 41(8):2260-8. PubMed: 21681738MGI: J:176811