Genomes and Genes
Gene Symbol: Ifngr1
Description: interferon gamma receptor 1
Alias: CD119, IFN-gammaR, Ifgr, Ifngr, Nktar, interferon gamma receptor 1, IFN-gamma receptor 1, IFN-gamma-R-alpha, IFN-gamma-R1, INF-g receptor, interferon gamma receptor alpha-chain
- Harrington L, Hatton R, Mangan P, Turner H, Murphy T, Murphy K, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123-32 pubmed..These findings provide a basis for understanding how inhibition of IFN-gamma signaling enhances development of pathogenic T(H)-17 effector cells that can exacerbate autoimmunity. ..
- Axtell R, de Jong B, Boniface K, van der Voort L, Bhat R, De Sarno P, et al. T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat Med. 2010;16:406-12 pubmed publisher..Hence, IFN-beta is proinflammatory in T(H)17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-beta. ..
- Dunn G, Bruce A, Sheehan K, Shankaran V, Uppaluri R, Bui J, et al. A critical function for type I interferons in cancer immunoediting. Nat Immunol. 2005;6:722-9 pubmed..Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma. ..
- Muller U, Steinhoff U, Reis L, Hemmi S, Pavlovic J, Zinkernagel R, et al. Functional role of type I and type II interferons in antiviral defense. Science. 1994;264:1918-21 pubmed..Comparison of mice lacking either type I or type II IFN receptors showed that, at least in response to some viruses, both IFN systems are essential for antiviral defense and are functionally nonredundant. ..
- Pinschewer D, Flatz L, Steinborn R, Horvath E, Fernandez M, Lutz H, et al. Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes. Int Immunol. 2010;22:749-56 pubmed publisher..These results provide a better understanding of the immunobiology of rLCMV/VSVG and will contribute to the further development of GP exchange vaccines for combating arenaviral hemorrhagic fevers. ..
- Ashkar A, Di Santo J, Croy B. Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J Exp Med. 2000;192:259-70 pubmed
- Vollstedt S, Arnold S, Schwerdel C, Franchini M, Alber G, Di Santo J, et al. Interplay between alpha/beta and gamma interferons with B, T, and natural killer cells in the defense against herpes simplex virus type 1. J Virol. 2004;78:3846-50 pubmed..These results suggest that distinct and essential immune elements are recruited in a time-dependent fashion to control acute and persistent HSV-1 infection. ..
- Tewari K, Nakayama Y, Suresh M. Role of direct effects of IFN-gamma on T cells in the regulation of CD8 T cell homeostasis. J Immunol. 2007;179:2115-25 pubmed..These findings have clarified fundamental features of control of T cell homeostasis by IFN-gamma in the context of CD8 T cell memory and protective immunity...
- Schijns V, Haagmans B, Wierda C, Kruithof B, Heijnen I, Alber G, et al. Mice lacking IL-12 develop polarized Th1 cells during viral infection. J Immunol. 1998;160:3958-64 pubmed..Our data suggest that viruses may selectively induce IFN-gamma production and Th1-type immune reactions even in the absence of IL-12. ..
- Turner S, Olivas E, Gutierrez A, Diaz G, Doherty P. Disregulated influenza A virus-specific CD8+ T cell homeostasis in the absence of IFN-gamma signaling. J Immunol. 2007;178:7616-22 pubmed..A virus infection of mice deficient for IFN-gamma (IFN-gamma(-/-)) or deficient for the IFN-gamma receptor 1 (IFNGR1(-/-)) was, when compared with the wild-type (WT) B6 controls, associated with increased Ag-specific CD8+ T cell ..
- Marsters S, Pennica D, Bach E, Schreiber R, Ashkenazi A. Interferon gamma signals via a high-affinity multisubunit receptor complex that contains two types of polypeptide chain. Proc Natl Acad Sci U S A. 1995;92:5401-5 pubmed
- Eriksson U, Kurrer M, Bingisser R, Eugster H, Saremaslani P, Follath F, et al. Lethal autoimmune myocarditis in interferon-gamma receptor-deficient mice: enhanced disease severity by impaired inducible nitric oxide synthase induction. Circulation. 2001;103:18-21 pubmed..Our data provide evidence that IFN-gamma protects mice from lethal autoimmune myocarditis by inducing the expression of inducible nitric oxide synthase followed by the downregulation of T-cell responses. ..
- Baldridge M, King K, Boles N, Weksberg D, Goodell M. Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature. 2010;465:793-7 pubmed publisher..Our studies contribute to a deeper understanding of haematological responses in patients with chronic infections such as HIV/AIDS or tuberculosis. ..
- Prestwood T, Morar M, Zellweger R, Miller R, May M, Yauch L, et al. Gamma interferon (IFN-?) receptor restricts systemic dengue virus replication and prevents paralysis in IFN-?/? receptor-deficient mice. J Virol. 2012;86:12561-70 pubmed publisher..These results demonstrate the roles of IFN-?R signaling in protection from initial systemic and subsequent CNS disease following DENV infection and demonstrate the importance of CD8(+) T cells in preventing DENV-induced CNS disease...
- Qin Z, Blankenstein T. CD4+ T cell--mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN gamma receptor expression by nonhematopoietic cells. Immunity. 2000;12:677-86 pubmed..This shows that an effective anti-tumor response involves communication between CD4+ T cells and nonhematopoietic cells, most likely within the tumor stroma, and that tumor immunity must not entirely rely on direct tumor cell killing. ..
- Desvignes L, Ernst J. Interferon-gamma-responsive nonhematopoietic cells regulate the immune response to Mycobacterium tuberculosis. Immunity. 2009;31:974-85 pubmed publisher..These results reveal a previously unsuspected role for IFN-gamma responsiveness in nonhematopoietic cells in regulation of immunity to M. tuberculosis and illustrate the role of IDO in the inhibition of Th17 cell responses...
- Belyaev N, Brown D, Diaz A, Rae A, Jarra W, Thompson J, et al. Induction of an IL7-R(+)c-Kit(hi) myelolymphoid progenitor critically dependent on IFN-gamma signaling during acute malaria. Nat Immunol. 2010;11:477-85 pubmed publisher..Thus, IFN-gamma is a key modulator of hematopoiesis and innate and adaptive immunity during acute malaria infection...
- Mikhak Z, Farsidjani A, Luster A. Endotoxin augmented antigen-induced Th1 cell trafficking amplifies airway neutrophilic inflammation. J Immunol. 2009;182:7946-56 pubmed publisher..This reciprocal interaction between LPS and Ag-activated Th1 cells represents a collaborative connection between the innate and adaptive arms of the immune system. ..
- Ou R, Zhou S, Huang L, Moskophidis D. Critical role for alpha/beta and gamma interferons in persistence of lymphocytic choriomeningitis virus by clonal exhaustion of cytotoxic T cells. J Virol. 2001;75:8407-23 pubmed..We discuss the role of IFNs in influencing virus-specific T cells that determine the outcome of persistent infections. ..
- Maldonado R, Soriano M, Perdomo L, Sigrist K, Irvine D, Decker T, et al. Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse. J Exp Med. 2009;206:877-92 pubmed publisher..ligation, TCR stimuli induce the translocation of signal transducer and activator of transcription 1 (STAT1) to IFNGR1-rich regions of the membrane...
- Kamijo R, Le J, Shapiro D, Havell E, Huang S, Aguet M, et al. Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guérin and subsequent challenge with lipopolysaccharide. J Exp Med. 1993;178:1435-40 pubmed
- Kamijo R, Shapiro D, Le J, Huang S, Aguet M, Vilcek J. Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon gamma receptor. Proc Natl Acad Sci U S A. 1993;90:6626-30 pubmed..The inability of other cytokines to substitute fully for IFN-gamma in macrophage activation helps to explain the earlier observed decreased resistance of IFN-gamma R0/0 mice to some infections. ..
- Gil M, Bohn E, O Guin A, Ramana C, Levine B, Stark G, et al. Biologic consequences of Stat1-independent IFN signaling. Proc Natl Acad Sci U S A. 2001;98:6680-5 pubmed..Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences. ..
- Szente B, Subramaniam P, Johnson H. Identification of IFN-gamma receptor binding sites for JAK2 and enhancement of binding by IFN-gamma and its C-terminal peptide IFN-gamma(95-133). J Immunol. 1995;155:5617-22 pubmed..Furthermore, the data support previous studies that demonstrated that intracellular IFN-gamma plays a role in cell activation. ..
- Durbin J, Johnson T, Durbin R, Mertz S, Morotti R, Peebles R, et al. The role of IFN in respiratory syncytial virus pathogenesis. J Immunol. 2002;168:2944-52 pubmed..These findings suggest that STAT1 activation by both type I (alphabeta) and type II (gamma) IFNs plays an important role in establishing a protective, Th1 Ag-specific immune response to RSV infection. ..
- Gondek D, Roan N, Starnbach M. T cell responses in the absence of IFN-gamma exacerbate uterine infection with Chlamydia trachomatis. J Immunol. 2009;183:1313-9 pubmed publisher..Thus, we demonstrate that the secretion of IFN-gamma is necessary for protection against C. trachomatis and that in the absence of host cell IFN-gammaR expression, both Th1 and Th2 cells lead to increased burden of C. trachomatis. ..
- Zhu J, Jankovic D, Oler A, Wei G, Sharma S, Hu G, et al. The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses. Immunity. 2012;37:660-73 pubmed publisher..Our study revealed redundancy and synergy among several Th1 cell-inducing pathways in regulating the expression of T-bet and IFN-Î³, and a critical role of T-bet in suppressing an endogenous Th2 cell-associated program. ..
- Shankaran V, Ikeda H, Bruce A, White J, Swanson P, Old L, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410:1107-11 pubmed..However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals...
- Muranski P, Boni A, Antony P, Cassard L, Irvine K, Kaiser A, et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood. 2008;112:362-73 pubmed publisher..This principle should be considered in designing clinical trials involving adoptive transfer-based immunotherapy of human malignancies. ..
- Rocha V, Folco E, Sukhova G, Shimizu K, Gotsman I, Vernon A, et al. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ Res. 2008;103:467-76 pubmed publisher..These results indicate a role for T cells and IFNgamma, a prototypical T-helper 1 cytokine, in regulation of the inflammatory response that accompanies obesity. ..
- Flórido M, Pearl J, Solache A, Borges M, Haynes L, Cooper A, et al. Gamma interferon-induced T-cell loss in virulent Mycobacterium avium infection. Infect Immun. 2005;73:3577-86 pubmed
- Maldonado R, Irvine D, Schreiber R, Glimcher L. A role for the immunological synapse in lineage commitment of CD4 lymphocytes. Nature. 2004;431:527-32 pubmed..The interferon-gamma (IFNGR) and interleukin 4 (IL-4R) cytokine receptors, in particular, direct the earliest stages of T-helper commitment...
- Tsuji M, Miyahira Y, Nussenzweig R, Aguet M, Reichel M, Zavala F. Development of antimalaria immunity in mice lacking IFN-gamma receptor. J Immunol. 1995;154:5338-44 pubmed..However, the nature of the anti-parasite mechanism(s) changes in the course of immunization, so that multiple immunizing doses elicit additional protective mechanisms, which are independent of IFN-gamma and its receptor...
- Ebrahimi B, Dutia B, Brownstein D, Nash A. Murine gammaherpesvirus-68 infection causes multi-organ fibrosis and alters leukocyte trafficking in interferon-gamma receptor knockout mice. Am J Pathol. 2001;158:2117-25 pubmed..These changes suggest a role for dysregulated cytokines and chemokines in severe organ-specific fibrosis with implications for immune-mediated fibrotic disorders. ..
- Manoury Schwartz B, Chiocchia G, Bessis N, Abehsira Amar O, Batteux F, Muller S, et al. High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors. J Immunol. 1997;158:5501-6 pubmed
- Tsai C, Kai J, Huang W, Wang C, Wang Y, Chen C, et al. Glycogen synthase kinase-3beta facilitates IFN-gamma-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2. J Immunol. 2009;183:856-64 pubmed publisher..All these results showed that activated GSK-3beta synergistically affected IFN-gamma-induced STAT1 activation by inhibiting SHP2. ..
- Cantin E, Tanamachi B, Openshaw H, Mann J, Clarke K. Gamma interferon (IFN-gamma) receptor null-mutant mice are more susceptible to herpes simplex virus type 1 infection than IFN-gamma ligand null-mutant mice. J Virol. 1999;73:5196-200 pubmedMouse strains with null mutations in the gamma interferon gene (Ifng) or the gamma interferon receptor gene (Ifngr) have been engineered...
- Batten M, Li J, Yi S, Kljavin N, Danilenko D, Lucas S, et al. Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat Immunol. 2006;7:929-36 pubmed..Finally, IL-27 suppressed IL-6-mediated T cell proliferation. These data provide a mechanistic explanation for the IL-27-mediated immune suppression noted in several in vivo models of inflammation. ..
- Lee C, Rao D, Gertner R, Gimeno R, Frey A, Levy D. Distinct requirements for IFNs and STAT1 in NK cell function. J Immunol. 2000;165:3571-7 pubmed..These results demonstrate that both IFN-alpha and IFN-gamma are required to maintain NK cell function and define a STAT1-dependent but partially IFN-independent pathway required for NK-mediated antitumor activity. ..
- Shresta S, Kyle J, Snider H, Basavapatna M, Beatty P, Harris E. Interferon-dependent immunity is essential for resistance to primary dengue virus infection in mice, whereas T- and B-cell-dependent immunity are less critical. J Virol. 2004;78:2701-10 pubmed
- Kamijo R, Gerecitano J, Shapiro D, Green S, Aguet M, Le J, et al. Generation of nitric oxide and clearance of interferon-gamma after BCG infection are impaired in mice that lack the interferon-gamma receptor. J Inflamm. 1995;46:23-31 pubmed
- Schulz E, Mariani L, Radbruch A, Hofer T. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Immunity. 2009;30:673-83 pubmed publisher..Thus initial polarization and subsequent imprinting of Th1 cells are mediated by interlinked, sequentially acting positive feedback loops of TCR-interferon-gamma-Stat1-T-bet and interleukin-12-Stat4-T-bet signaling. ..
- Swihart K, Fruth U, Messmer N, Hug K, Behin R, Huang S, et al. Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response. J Exp Med. 1995;181:961-71 pubmed..These data show that even in the absence of IFN-gamma receptors, T helper cell (Th) 1-type responses still develop in genetically resistant mice with no evidence for the expansion of Th2 cells. ..
- Mizuno T, Zhang G, Takeuchi H, Kawanokuchi J, Wang J, Sonobe Y, et al. Interferon-gamma directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-gamma receptor and AMPA GluR1 receptor. FASEB J. 2008;22:1797-806 pubmed publisher..These findings provide novel mechanisms of neuronal excitotoxicity, which may occur in both inflammatory and neurodegenerative diseases in the CNS. ..
- Hess J, Ladel C, Miko D, Kaufmann S. Salmonella typhimurium aroA- infection in gene-targeted immunodeficient mice: major role of CD4+ TCR-alpha beta cells and IFN-gamma in bacterial clearance independent of intracellular location. J Immunol. 1996;156:3321-6 pubmed..typhimurium SL7207 Hlys and control strains did not differ in beta 2m-/- mutants. This finding argues against direct correlation of cytosolic location of S. typhimurium SL7207 Hlys with CD8+ T cell dependency of protection. ..
- Haring J, Badovinac V, Olson M, Varga S, Harty J. In vivo generation of pathogen-specific Th1 cells in the absence of the IFN-gamma receptor. J Immunol. 2005;175:3117-22 pubmed..Thus, both chains of the IFN-gammaR are dispensable for the generation of Th1 Ag-specific CD4 T cells after infection in vivo. ..
- Schijns V, Haagmans B, Rijke E, Huang S, Aguet M, Horzinek M. IFN-gamma receptor-deficient mice generate antiviral Th1-characteristic cytokine profiles but altered antibody responses. J Immunol. 1994;153:2029-37 pubmed..However, it profoundly impairs the generation of protective antiviral Ab. ..
- Ashkar A, Croy B. Interferon-gamma contributes to the normalcy of murine pregnancy. Biol Reprod. 1999;61:493-502 pubmed..Furthermore, evidence is presented that IFN-gamma-producing cells exist in mesometrial regions of implantation sites that are neither NK nor T cells. ..
- MacNamara K, Oduro K, Martin O, Jones D, McLaughlin M, Choi K, et al. Infection-induced myelopoiesis during intracellular bacterial infection is critically dependent upon IFN-? signaling. J Immunol. 2011;186:1032-43 pubmed publisher..We propose that, in addition to its many other known roles, IFN-? acts to control infection by directly promoting the differentiation of myeloid cells that contribute to host defense. ..
- Fiette L, Aubert C, Muller U, Huang S, Aguet M, Brahic M, et al. Theiler's virus infection of 129Sv mice that lack the interferon alpha/beta or interferon gamma receptors. J Exp Med. 1995;181:2069-76 pubmed..They also lend support to the notion that the Ifg gene is involved in the resistance/susceptibility of inbred strains of mice to persistent infection by this picornavirus. ..
- 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. ..
- van den Broek M, Muller U, Huang S, Aguet M, Zinkernagel R. Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors. J Virol. 1995;69:4792-6 pubmed..Even though global antiviral immunoglobulin G (IgG) titers were within normal ranges, the IgG subclass distribution was heavily biased toward IgG1. ..
- Willenborg D, Fordham S, Bernard C, Cowden W, Ramshaw I. IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J Immunol. 1996;157:3223-7 pubmed..These results indicate that IFN-gamma is not essential for the generation or function of anti-MOG35-55 effector cells but does play an important role in down-regulating EAE at both the effector and induction phase of disease. ..
- Rhee S, Walker W, Cherayil B. Developmentally regulated intestinal expression of IFN-gamma and its target genes and the age-specific response to enteric Salmonella infection. J Immunol. 2005;175:1127-36 pubmed..typhimurium infection resembled that of the wild-type pups. Our findings thus reveal a novel role for IFN-gamma in the developmental regulation of antimicrobial responses in the intestine. ..
- Schijns V, Wierda C, van Hoeij M, Horzinek M. Exacerbated viral hepatitis in IFN-gamma receptor-deficient mice is not suppressed by IL-12. J Immunol. 1996;157:815-21 pubmed..Furthermore, they emphasize the pivotal antiviral role of IFN-gamma in protection against acute coronavirus-induced hepatitis. ..
- Huang S, Hendriks W, Althage A, Hemmi S, Bluethmann H, Kamijo R, et al. Immune response in mice that lack the interferon-gamma receptor. Science. 1993;259:1742-5 pubmed..These mutant mice offer the possibility for the further elucidation of IFN-gamma-mediated functions by transgenic cell- or tissue-specific reconstitution of a functional receptor. ..
- Car B, Eng V, Schnyder B, Ozmen L, Huang S, Gallay P, et al. Interferon gamma receptor deficient mice are resistant to endotoxic shock. J Exp Med. 1994;179:1437-44 pubmed
- Lee C, Gimeno R, Levy D. Differential regulation of constitutive major histocompatibility complex class I expression in T and B lymphocytes. J Exp Med. 1999;190:1451-64 pubmed
- Dal Canto A, Swanson P, O Guin A, Speck S, Virgin H. IFN-gamma action in the media of the great elastic arteries, a novel immunoprivileged site. J Clin Invest. 2001;107:R15-22 pubmed..These concepts have significant implications for understanding immune responses contributing to or controlling chronic inflammatory diseases of the great vessels. ..
- 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. ..
- Vermeire K, Heremans H, Vandeputte M, Huang S, Billiau A, Matthys P. Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice. J Immunol. 1997;158:5507-13 pubmed..The data are in line with the concept of a pathogenic role of Th1-type cellular immunity in CIA in spite of a decreased Ab response to collagen type II. ..
- 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