Genomes and Genes
Gene Symbol: Ifng
Description: interferon gamma
Alias: IFN-g, Ifg, interferon gamma, IFN-gamma, gamma interferon
- Reid Yu S, Small C, Coombes B. CD3⁻NK1.1⁺ cells aid in the early induction of a Th1 response to an attaching and effacing enteric pathogen. Eur J Immunol. 2013;43:2638-49 pubmed publisher..rodentium IgG in NK1.1-depleted mice. These data establish that CD3⁻NK1.1⁺ cells are critical for inducing an early Th1 response involved in clearance of a pathogen that is restricted to the gastrointestinal tract. ..
- Gomez J, Wapinski O, Yang Y, Bureau J, Gopinath S, Monack D, et al. The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-γ locus. Cell. 2013;152:743-54 pubmed publisher..Thus, this lncRNA regulates epigenetic marking of IFN-γ-encoding chromatin, expression of IFN-γ, and susceptibility to a viral and a bacterial pathogen. ..
- Ouyang W, Liao W, Luo C, Yin N, Huse M, Kim M, et al. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature. 2012;491:554-9 pubmed publisher..analysis of Foxo1 binding sites reveals ~300 Foxo1-bound target genes, including the pro-inflammatory cytokine Ifng, that do not seem to be directly regulated by Foxp3...
- Mishra B, Rathinam V, Martens G, Martinot A, Kornfeld H, Fitzgerald K, et al. Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1β. Nat Immunol. 2013;14:52-60 pubmed publisher..Our data indicate that the NO produced as a result of adaptive immunity is indispensable in modulating the destructive innate inflammatory responses elicited during persistent infections. ..
- Lu Y, Hong S, Li H, Park J, Hong B, Wang L, et al. Th9 cells promote antitumor immune responses in vivo. J Clin Invest. 2012;122:4160-71 pubmed publisher..Our data suggest a distinct role for tumor-specific Th9 cells in provoking CD8+ CTL-mediated antitumor immunity and indicate that Th9 cell-based cancer immunotherapy may be a promising therapeutic approach. ..
- Hsieh M, Lai S, Chen J, Sung J, Lin Y, Wu Hsieh B, et al. Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. J Immunol. 2006;177:1855-63 pubmed..Our results suggest that both CXCR3 and CXCL10/IP-10 contribute to resistance against primary dengue virus infection and that chemokines that are indistinguishable in in vitro assays differ in their activities in vivo. ..
- Hu Y, Hu X, Boumsell L, Ivashkiv L. IFN-gamma and STAT1 arrest monocyte migration and modulate RAC/CDC42 pathways. J Immunol. 2008;180:8057-65 pubmed..Crosstalk between Jak-STAT and Rac/Cdc42 GTPase-mediated signaling pathways provides a molecular mechanism by which cytokines can regulate cell migration. ..
- Sardinha L, Elias R, Mosca T, Bastos K, Marinho C, D Império Lima M, et al. Contribution of NK, NK T, gamma delta T, and alpha beta T cells to the gamma interferon response required for liver protection against Trypanosoma cruzi. Infect Immun. 2006;74:2031-42 pubmed..The presence of numerous intrahepatic amastigotes in infected gamma interferon (IFN-gamma)-deficient mice corroborates the notion that the liver is protected by an efficient local immunity...
- Wysocka M, Kubin M, Vieira L, Ozmen L, Garotta G, Scott P, et al. Interleukin-12 is required for interferon-gamma production and lethality in lipopolysaccharide-induced shock in mice. Eur J Immunol. 1995;25:672-6 pubmed..Thus, IL-12 is required for IFN-gamma production and lethality in an endotoxic shock model in mice. ..
- Quezada S, Simpson T, Peggs K, Merghoub T, Vider J, Fan X, et al. Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med. 2010;207:637-50 pubmed publisher....
- Naka T, Tsutsui H, Fujimoto M, Kawazoe Y, Kohzaki H, Morita Y, et al. SOCS-1/SSI-1-deficient NKT cells participate in severe hepatitis through dysregulated cross-talk inhibition of IFN-gamma and IL-4 signaling in vivo. Immunity. 2001;14:535-45 pubmed....
- Rodriguez F, Harkins S, Slifka M, Whitton J. Immunodominance in virus-induced CD8(+) T-cell responses is dramatically modified by DNA immunization and is regulated by gamma interferon. J Virol. 2002;76:4251-9 pubmed..demonstrate that subdominant responses are actively suppressed by dominant CD8(+) T-cell responses and that gamma interferon (IFN-gamma) is required for this suppression...
- Soutto M, Zhang F, Enerson B, Tong Y, Boothby M, Aune T. A minimal IFN-gamma promoter confers Th1 selective expression. J Immunol. 2002;169:4205-12 pubmed..Together, the results demonstrate that a minimal IFN-gamma promoter contains a T box expressed in T cells responsive unit and is sufficient to confer Th1 selective expression upon a reporter. ..
- Feng C, Zheng L, Jankovic D, Bafica A, Cannons J, Watford W, et al. The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death. Nat Immunol. 2008;9:1279-87 pubmed publisher..Our studies identify a feedback mechanism in the T helper type 1 response that limits the detrimental effects of IFN-gamma on effector T lymphocyte survival while promoting the antimicrobial functions of IFN-gamma. ..
- Verri W, Cunha T, Parada C, Wei X, Ferreira S, Liew F, et al. IL-15 mediates immune inflammatory hypernociception by triggering a sequential release of IFN-gamma, endothelin, and prostaglandin. Proc Natl Acad Sci U S A. 2006;103:9721-5 pubmed....
- Speyer C, Neff T, Warner R, Guo R, Sarma J, Riedemann N, et al. Regulatory effects of iNOS on acute lung inflammatory responses in mice. Am J Pathol. 2003;163:2319-28 pubmed..In vitro stimulation of microvascular endothelial cells with LPS and IFN gamma revealed elevated production of CXC and CC chemokines in cells from iNOS(-/-) mice when compared to endothelial ..
- Zou J, Yamamoto N, Fujii T, Takenaka H, Kobayashi M, Herrmann S, et al. Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-gamma production by anti-tumor T cells. Int Immunol. 1995;7:1135-45 pubmed....
- Jain R, Tartar D, Gregg R, Divekar R, Bell J, Lee H, et al. Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production. J Exp Med. 2008;205:207-18 pubmed publisher..GAD2) represents a late-stage epitope, but GAD2-specific T cell receptor transgenic T cells producing interferon gamma (IFNgamma) protect against passive TID...
- Perona Wright G, Mohrs K, Mayer K, Mohrs M. Differential regulation of IL-4Ralpha expression by antigen versus cytokine stimulation characterizes Th2 progression in vivo. J Immunol. 2010;184:615-23 pubmed publisher..Together these data reveal a tightly controlled program of changing IL-4 responsiveness that characterizes the initiation, amplification, and restriction of a Th2 response in vivo. ..
- Banaiee N, Kincaid E, Buchwald U, Jacobs W, Ernst J. Potent inhibition of macrophage responses to IFN-gamma by live virulent Mycobacterium tuberculosis is independent of mature mycobacterial lipoproteins but dependent on TLR2. J Immunol. 2006;176:3019-27 pubmed..These results establish that M. tuberculosis possesses multiple mechanisms of inhibiting responses to IFN-gamma. ..
- Doodes P, Cao Y, Hamel K, Wang Y, Rodeghero R, Mikecz K, et al. IFN-gamma regulates the requirement for IL-17 in proteoglycan-induced arthritis. J Immunol. 2010;184:1552-9 pubmed publisher..These results demonstrate that both IFN-gamma and IL-17 have the potential to induce PGIA, but it is the strength of the IFN-gamma response that regulates the contribution of each of these Th effector cytokines to disease. ..
- Campos R, Szczepanik M, Itakura A, Akahira Azuma M, Sidobre S, Kronenberg M, et al. Cutaneous immunization rapidly activates liver invariant Valpha14 NKT cells stimulating B-1 B cells to initiate T cell recruitment for elicitation of contact sensitivity. J Exp Med. 2003;198:1785-96 pubmed....
- Nansen A, Jensen T, Christensen J, Andreasen S, Ropke C, Marker O, et al. Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus. J Immunol. 1999;163:6114-22 pubmed..Thus, the presence or absence of IFN-gamma determines whether CTLs will clear infection with this noncytopathogenic virus or induce severe immunopathology. ..
- Harty J, Bevan M. Specific immunity to Listeria monocytogenes in the absence of IFN gamma. Immunity. 1995;3:109-17 pubmed..We demonstrate that resistance of IFN gamma gene knockout (GKO-/-) mice to the intracellular bacterium Listeria monocytogenes is severely impaired compared ..
- Hansen D, Bernard N, Nie C, Schofield L. NK cells stimulate recruitment of CXCR3+ T cells to the brain during Plasmodium berghei-mediated cerebral malaria. J Immunol. 2007;178:5779-88 pubmed....
- Kronenberg K, Brosch S, Butsch F, Tada Y, Shibagaki N, Udey M, et al. Vaccination with TAT-antigen fusion protein induces protective, CD8(+) T cell-mediated immunity against Leishmania major. J Invest Dermatol. 2010;130:2602-10 pubmed publisher....
- Rodriguez M, Zoecklein L, Howe C, Pavelko K, Gamez J, Nakane S, et al. Gamma interferon is critical for neuronal viral clearance and protection in a susceptible mouse strain following early intracranial Theiler's murine encephalomyelitis virus infection. J Virol. 2003;77:12252-65 pubmedWe evaluated the role of gamma interferon (IFN-gamma) in protecting neurons from virus-induced injury following central nervous system infection...
- Bouley D, Kanangat S, Wire W, Rouse B. Characterization of herpes simplex virus type-1 infection and herpetic stromal keratitis development in IFN-gamma knockout mice. J Immunol. 1995;155:3964-71 pubmed....
- Berner V, Liu H, Zhou Q, Alderson K, Sun K, Weiss J, et al. IFN-gamma mediates CD4+ T-cell loss and impairs secondary antitumor responses after successful initial immunotherapy. Nat Med. 2007;13:354-60 pubmed..Thus, although immunotherapeutic regimens inducing strong IFN-gamma responses can lead to successful early antitumor efficacy, they may also impair the development of durable antitumor responses. ..
- Ilangumaran S, Ramanathan S, Ning T, La Rose J, Reinhart B, Poussier P, et al. Suppressor of cytokine signaling 1 attenuates IL-15 receptor signaling in CD8+ thymocytes. Blood. 2003;102:4115-22 pubmed..Because many different cell types express IL-15, our results strongly suggest that SOCS1 functions as an indispensable attenuator of IL-15 receptor signaling in developing CD8+ thymocytes. ..
- McLoughlin R, Witowski J, Robson R, Wilkinson T, Hurst S, Williams A, et al. Interplay between IFN-gamma and IL-6 signaling governs neutrophil trafficking and apoptosis during acute inflammation. J Clin Invest. 2003;112:598-607 pubmed..These data emphasize a pivotal role for IFN-gamma in regulating innate immunity through control of both the recruitment and clearance phases of PMN trafficking. ..
- Burdeinick Kerr R, Wind J, Griffin D. Synergistic roles of antibody and interferon in noncytolytic clearance of Sindbis virus from different regions of the central nervous system. J Virol. 2007;81:5628-36 pubmed....
- Wang Z, Hong J, Sun W, Xu G, Li N, Chen X, et al. Role of IFN-gamma in induction of Foxp3 and conversion of CD4+ CD25- T cells to CD4+ Tregs. J Clin Invest. 2006;116:2434-41 pubmed..These findings have important implications for the understanding of the complex role of IFN-gamma in both induction and self regulation of inflammatory processes. ..
- Stange J, Hepworth M, Rausch S, Zajic L, Kuhl A, Uyttenhove C, et al. IL-22 mediates host defense against an intestinal intracellular parasite in the absence of IFN-γ at the cost of Th17-driven immunopathology. J Immunol. 2012;188:2410-8 pubmed publisher....
- Serreze D, Chapman H, Post C, Johnson E, Suarez Pinzon W, Rabinovitch A. Th1 to Th2 cytokine shifts in nonobese diabetic mice: sometimes an outcome, rather than the cause, of diabetes resistance elicited by immunostimulation. J Immunol. 2001;166:1352-9 pubmed....
- Aliberti J, Souto J, Marino A, Lannes Vieira J, Teixeira M, Farber J, et al. Modulation of chemokine production and inflammatory responses in interferon-gamma- and tumor necrosis factor-R1-deficient mice during Trypanosoma cruzi infection. Am J Pathol. 2001;158:1433-40 pubmed..cruzi infection and mediate resistance to infection. ..
- Awasthi A, Carrier Y, Peron J, Bettelli E, Kamanaka M, Flavell R, et al. A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol. 2007;8:1380-9 pubmed..Thus, IL-27 and transforming growth factor-beta promote the generation of IL-10-producing Tr1 cells. ..
- Rijneveld A, Lauw F, Schultz M, Florquin S, te Velde A, Speelman P, et al. The role of interferon-gamma in murine pneumococcal pneumonia. J Infect Dis. 2002;185:91-7 pubmed..These data suggest that endogenous IFN-gamma, despite its protective role in defense against intracellular pathogens, does not serve a protective role during pneumococcal pneumonia. ..
- Lovett Racke A, Rocchini A, Choy J, Northrop S, Hussain R, Ratts R, et al. Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. Immunity. 2004;21:719-31 pubmed..Since T-bet regulates IFNgamma production in CD4(+) T cells, but to a lesser extent in most other IFNgamma-producing cells, T-bet may be a target for therapeutics for Th1-mediated diseases. ..
- Reboldi A, Coisne C, Baumjohann D, Benvenuto F, Bottinelli D, Lira S, et al. C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol. 2009;10:514-23 pubmed publisher..Our results identify distinct molecular requirements and ports of lymphocyte entry into uninflamed versus inflamed CNS and suggest that the CCR6-CCL20 axis in the choroid plexus controls immune surveillance of the CNS. ..
- Wang S, Fan Y, Brunham R, Yang X. IFN-gamma knockout mice show Th2-associated delayed-type hypersensitivity and the inflammatory cells fail to localize and control chlamydial infection. Eur J Immunol. 1999;29:3782-92 pubmed..Moreover, the data suggest that the IFN-gamma KO mouse is a useful model system for studying chlamydial pathogenesis. ..
- Tishon A, Lewicki H, Rall G, Von Herrath M, Oldstone M. An essential role for type 1 interferon-gamma in terminating persistent viral infection. Virology. 1995;212:244-50 pubmed..In addition to the requirement for IFN-gamma, CD4+ T cells are essential for maintaining a CD8(+)-mediated cure of persistent viral infection. ..
- Alexander W, Starr R, Fenner J, Scott C, Handman E, Sprigg N, et al. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell. 1999;98:597-608 pubmed..In this study, SOCS1-/- mice were shown to exhibit excessive responses typical of those induced by interferon gamma (IFNgamma), were hyperresponsive to viral infection, and yielded macrophages with an enhanced IFNgamma-..
- Satoh Takayama N, Vosshenrich C, Lesjean Pottier S, Sawa S, Lochner M, Rattis F, et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity. 2008;29:958-70 pubmed publisher..RORgammat-driven diversification of intestinal NKp46+ cells thereby specifies an innate cellular defense mechanism that operates at mucosal surfaces...
- Cheng M, Nguyen M, Fantuzzi G, Koh T. Endogenous interferon-gamma is required for efficient skeletal muscle regeneration. Am J Physiol Cell Physiol. 2008;294:C1183-91 pubmed publisher..In summary, our results indicate that IFN-gamma promotes muscle healing, in part, by stimulating formation of new muscle fibers. ..
- Zhang H, Azimullah S, Zheng X, Wang X, Amir N, Mensah Brown E, et al. IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response. J Neuroimmunol. 2012;246:18-26 pubmed publisher..In conclusion, IFN-γ deficiency exacerbates EAN via upregulating Th17 cells despite a mitigated systemic Th1 immune response. ..
- Hegazy A, Peine M, Helmstetter C, Panse I, Fröhlich A, Bergthaler A, et al. Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. Immunity. 2010;32:116-28 pubmed publisher..Stable coexpression of GATA-3 and T-bet provides a molecular concept for the long-term coexistence of Th2 and Th1 cell lineage characteristics in single memory T cells. ..
- Yang Y, Ochando J, Bromberg J, Ding Y. Identification of a distant T-bet enhancer responsive to IL-12/Stat4 and IFNgamma/Stat1 signals. Blood. 2007;110:2494-500 pubmed..Together, we provide a novel mechanism for T-bet regulation, and suggest that IL-12/Stat4/T-bet play an important role in CD8 effector responses. ..
- Wozniak T, Saunders B, Ryan A, Britton W. Mycobacterium bovis BCG-specific Th17 cells confer partial protection against Mycobacterium tuberculosis infection in the absence of gamma interferon. Infect Immun. 2010;78:4187-94 pubmed publisher..Both gamma interferon (IFN-γ)- and interleukin 17 (IL-17)-secreting CD4(+) T cells have been identified in subjects with latent TB ..
- Taylor A, Murray H. Intracellular antimicrobial activity in the absence of interferon-gamma: effect of interleukin-12 in experimental visceral leishmaniasis in interferon-gamma gene-disrupted mice. J Exp Med. 1997;185:1231-9 pubmed..However, as judged by the effect of exogenous IL-12 this quiescent mechanism can readily be induced to rapidly yield enhanced intracellular antimicrobial activity. ..
- Lesinski G, Badgwell B, Zimmerer J, Crespin T, Hu Y, Abood G, et al. IL-12 pretreatments enhance IFN-alpha-induced Janus kinase-STAT signaling and potentiate the antitumor effects of IFN-alpha in a murine model of malignant melanoma. J Immunol. 2004;172:7368-76 pubmed..However, this treatment regimen did not significantly prolong the survival of IFN-gamma-deficient (B6.129S7-Ifng(tm1Ts)) mice compared with mice treated with IFN-alpha alone...
- Dalton D, Pitts Meek S, Keshav S, Figari I, Bradley A, Stewart T. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993;259:1739-42 pubmed..Resting splenic natural killer cell activity was reduced in IFN-gamma-deficient mice. Thus, IFN-gamma is essential for the function of several cell types of the murine immune system. ..
- Molesworth Kenyon S, Yin R, Oakes J, Lausch R. IL-17 receptor signaling influences virus-induced corneal inflammation. J Leukoc Biol. 2008;83:401-8 pubmed..Thus, IL-17 actively influences early virus-induced corneal inflammation. ..
- Kalis C, Gumenscheimer M, Freudenberg N, Tchaptchet S, Fejer G, Heit A, et al. Requirement for TLR9 in the immunomodulatory activity of Propionibacterium acnes. J Immunol. 2005;174:4295-300 pubmed..Because IFN-gamma is a key mediator of these effects, and enhanced IFN-gamma mRNA expression was absent in spleen and liver of P. acnes-primed TLR9(-/-) mice, we conclude that TLR9 is required for the induction of IFN-gamma by P. acnes. ..
- Simmons C, Goncalves N, Ghaem Maghami M, Bajaj Elliott M, Clare S, Neves B, et al. Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma. J Immunol. 2002;168:1804-12 pubmed..These studies are among the first to examine mechanisms of host resistance to an attaching-effacing pathogen and show an important role for IL-12 and IFN-gamma in limiting bacterial infection of the colonic epithelium. ..
- Andoh A, Masuda A, Yamakawa M, Kumazawa Y, Kasajima T. Absence of interleukin-4 enhances germinal center reaction in secondary immune response. Immunol Lett. 2000;73:35-41 pubmed..In conclusion, the absence of IL-4 enhanced GC reaction and specific antibody response of Th1-type. IL-4 may play an important role in inducing the appropriate magnitude of humoral immune response. ..
- Pai R, Pennini M, Tobian A, Canaday D, Boom W, Harding C. Prolonged toll-like receptor signaling by Mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Infect Immun. 2004;72:6603-14 pubmed..tuberculosis 19-kDa lipoprotein for >16 h inhibits gamma interferon (IFN-gamma)-induced major histocompatibility complex class II (MHC-II) expression by a mechanism involving ..
- Intlekofer A, Banerjee A, Takemoto N, Gordon S, Dejong C, Shin H, et al. Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science. 2008;321:408-11 pubmed publisher..T-bet and Eomes, thus, ensure that CD8+ T cells adopt an appropriate course of intracellular rather than extracellular destruction. ..
- Amante F, Haque A, Stanley A, Rivera F, Randall L, Wilson Y, et al. Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. J Immunol. 2010;185:3632-42 pubmed publisher..These findings provide novel insights into immune-mediated mechanisms of ECM pathogenesis and highlight the potential of T cells to both prevent and promote infectious diseases. ..
- Zimmerman M, Yang D, Hu X, Liu F, Singh N, Browning D, et al. IFN-γ upregulates survivin and Ifi202 expression to induce survival and proliferation of tumor-specific T cells. PLoS ONE. 2010;5:e14076 pubmed publisher..Our findings delineate a new role of the IFN-γ signaling pathway in regulating T cell proliferation and apoptosis through upregulating survivin and ifi202 expression. ..
- Feng C, Collazo Custodio C, Eckhaus M, Hieny S, Belkaid Y, Elkins K, et al. Mice deficient in LRG-47 display increased susceptibility to mycobacterial infection associated with the induction of lymphopenia. J Immunol. 2004;172:1163-8 pubmed..These findings establish a role for LRG-47 in host control of mycobacteria and demonstrate that in the context of the IFN-gamma response to persistent infection, LRG-47 can have downstream regulatory effects on lymphocyte survival. ..
- Tu S, Quante M, Bhagat G, Takaishi S, Cui G, Yang X, et al. IFN-γ inhibits gastric carcinogenesis by inducing epithelial cell autophagy and T-cell apoptosis. Cancer Res. 2011;71:4247-59 pubmed publisher....