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 |
|---|---|
|
N12F6
|
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-; IL-18KO; 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; Kajiwara Y; Leaf IA; Mao D; Ting JP; Coers J; Aderem A; Buxbaum JD; Miao EA. 2015. Canonical Inflammasomes Drive IFN-gamma to Prime Caspase-11 in Defense against a Cytosol-Invasive Bacterium. Cell Host Microbe 18(3):320-32. PubMed: 26320999MGI: J:243015
- 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
- Brown AS; Yang C; Fung KY; Bachem A; Bourges D; Bedoui S; Hartland EL; van Driel IR. 2016. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen. PLoS Pathog 12(6):e1005691. PubMed: 27300652MGI: J:245702
- 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
- Freeman L; Guo H; David CN; Brickey WJ; Jha S; Ting JP. 2017. NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes. J Exp Med 214(5):1351-1370. PubMed: 28404595MGI: J:242007
- 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
- Harms RZ; Creer AJ; Lorenzo-Arteaga KM; Ostlund KR; Sarvetnick NE. 2017. Interleukin (IL)-18 Binding Protein Deficiency Disrupts Natural Killer Cell Maturation and Diminishes Circulating IL-18. Front Immunol 8:1020. PubMed: 28900426MGI: J:255309
- 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
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