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Ifnar2  -  interferon (alpha and beta) receptor 2

Mus musculus

Synonyms: AI747302, IFN-R-2, IFN-alpha/beta receptor 2, Ifnar-2, Interferon alpha/beta receptor 2, ...
 
 
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Disease relevance of Ifnar2

  • Here, we examined the role of IFN-alpha/beta in the murine response to infection with Mycobacterium tuberculosis, using wildtype mice, mice with impaired signaling through the type I IFN receptor (IFNAR), and mice treated to reduce levels of type I IFNs [1].
  • Here we show that in vesicular stomatitis virus (VSV)-infected mouse embryonic fibroblasts (MEFs) the production of IFN-alpha is dependent on type I IFN receptor (IFNAR) triggering, whereas in infected mice early IFN-alpha production is IFNAR independent [2].
  • Mice lacking the IFNAR1 chain of the type I IFN receptor (IFNAR K/O mice) were immunized with a plasmid encoding glycoprotein C of pseudorabies virus (PRV-gC) [3].
  • Although mice deficient in either IFN regulatory factor (IRF)3 or the type I IFN receptor (IFNAR)1 are highly susceptible to viral infection, we show that these mice exhibit a profound resistance to infection caused by the Gram-positive intracellular bacterium Listeria monocytogenes compared with wild-type controls [4].
  • Lack of type I IFNR expression by P14 T cells did not affect cell division after LCMV infection but interfered with clonal expansion [5].
 

High impact information on Ifnar2

  • In this study, we addressed the role of type I IFNs by examining the infection of L. monocytogenes in BALB/c mice lacking the type I IFN receptor (IFN-alpha/betaR-/-) [6].
  • The replication of these viruses was examined in eyes and trigeminal ganglia for 1-7 d after corneal inoculation in mice with null mutations (-/-) in interferon receptors (IFNR) for type I IFNs (IFN-alpha/betaR), type II IFN (IFN-gammaR), and both type I and type II IFNs (IFN-alpha/beta/gammaR) [7].
  • CONCLUSION: Arthritis triggered by dsRNA is not dependent on the expression of the dsRNA-signaling molecule PKR (or Toll-like receptor 3, as previously shown), but is associated with the ability to produce type I IFN and is critically dependent on type I IFN receptor signaling [8].
  • Type I IFN receptor signals directly stimulate local B cells early following influenza virus infection [9].
  • Cutting edge: CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion [5].
 

Biological context of Ifnar2

  • Although the amino acid sequences of various IFN-alpha/beta subtypes differ markedly, they are all considered to share a common three-dimensional structure and to bind the same heterodimeric receptor, composed of the IFNAR-1 and IFNAR-2 subunits [10].
  • While DNA synthesis in CSF-1-stimulated BMM from normal mice was also very sensitive to the inhibitory actions of very low concentrations of added IFN-alpha beta, DNA synthesis in BMM from the "knockout" mice was not, indicating that the type I IFN receptor component containing the null mutation was essential for signal transduction [11].
  • A vector derived from a human Ad serotype (AdHu5) induced low levels of type I IFN following infection of dendritic cells (DCs) and stimulated normal transgene product-specific antibody responses in mice that have a defective type I IFN receptor (IFNAR(-/-)) [12].
  • IFNGR-2 is localized on chromosome 1 of chicken in tandem with IFNAR-1, interleukin- 10 receptor (IL-10R-2), and IFNAR-2 [13].
  • The serine kinase activity of the PI-3K was activated by human IFNalpha in these cells, suggesting that phosphorylation of the Type I IFN receptor is not essential for PI3K activation [14].
 

Anatomical context of Ifnar2

  • We used vaccine-induced, antiviral CD8(+) T cell responses in IFN-beta (IFN-beta(-/-))- or type I IFN receptor (IFNAR(-/-))-deficient mice to study immunomodulating effects of type I IFN that are not complicated by the interference of a concomitant virus infection [15].
  • The nature of the rearrangements affecting this gene in interferon-resistant (IFNR) L1210 mutant cell lines is described [16].
  • Thus, ligand(s) of the type I IFNR are direct nonredundant early innate signals that regulate local antiviral B cell responses [9].
  • Signaling through a pathway involving the type I IFN receptor and Stat1 sensitized macrophages to L. monocytogenes-induced cell death in a manner not requiring inducible NO synthase (nitric oxide synthase 2) or protein kinase R, potential effectors of type I IFN action during microbial infections [17].
  • This very early "activation" of such a high percentage of lymphocytes required the presence of type I IFN receptor genes, was inducible with poly(I:C), and correlated with IFN-I levels in serum [18].
 

Physical interactions of Ifnar2

  • These data indicate potential dual actions of soluble muIfnar-2 and imply that a signal can be transduced through the Ifnar-1 chain of the receptor complex in the absence of the cytoplasmic domain of Ifnar-2 [19].
 

Other interactions of Ifnar2

  • It was found that Ab to IFN-alpha beta could enhance the proliferative response in CSF-treated BMM that were able to respond to endogenous IFN-alpha beta; however, BMM from mice lacking a component of the type I IFN receptor did not show any enhancement of CSF-1-dependent DNA synthesis on addition of the Ab [11].
  • In mice deficient in the type I IFN receptor, imiquimod induced levels of IFN similar to those in control mice, but again, neither 2-5 OAS, IRF-1, nor IL-6 genes were induced in mutant mice [20].
  • Moreover, the levels of transgene expression following in vivo gene delivery were markedly increased in mice lacking functional type I IFN receptor genes, compared to wild-type mice or mice lacking IFN-gamma or TNF receptors [21].
  • In this report, we have used mice that are deficient in components of the early defence system, the common type I interferon (IFN) receptor (IFN R), the transcriptional activator IRF-1, and the inducible nitric oxide synthase, to investigate the contribution of these mechanisms to control of MHV-68 infection [22].
 

Analytical, diagnostic and therapeutic context of Ifnar2

  • The role of type I IFN signaling in CD8 T cells was analyzed in an adoptive transfer model using P14 TCR transgenic CD8 T cells specific for lymphocytic choriomeningitis virus (LCMV) but deficient in type I IFNR [5].
  • Here, it is shown that BRSV can replicate efficiently on primary cell cultures derived from type I IFN receptor-deficient, but not from wild-type IFN-competent, mice [23].
  • Importantly, we observed that virus-induced apoptosis was inhibited by anti-IFN-alpha/beta antibodies, and in cells lacking either the type I IFN receptor 1 (IFNAR1) or its downstream mediator, Stat1 (Signal transducer and activator of transcription 1) [24].
  • PEG-IFN-alpha2b induced a dose-dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor [25].

References

  1. Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak-Stat pathway. Manca, C., Tsenova, L., Freeman, S., Barczak, A.K., Tovey, M., Murray, P.J., Barry, C., Kaplan, G. J. Interferon Cytokine Res. (2005) [Pubmed]
  2. Virus-induced interferon alpha production by a dendritic cell subset in the absence of feedback signaling in vivo. Barchet, W., Cella, M., Odermatt, B., Asselin-Paturel, C., Colonna, M., Kalinke, U. J. Exp. Med. (2002) [Pubmed]
  3. Type I IFN modulates the immune response induced by DNA vaccination to pseudorabies virus glycoprotein C. Tudor, D., Riffault, S., Carrat, C., Lefèvre, F., Bernoin, M., Charley, B. Virology (2001) [Pubmed]
  4. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. O'Connell, R.M., Saha, S.K., Vaidya, S.A., Bruhn, K.W., Miranda, G.A., Zarnegar, B., Perry, A.K., Nguyen, B.O., Lane, T.F., Taniguchi, T., Miller, J.F., Cheng, G. J. Exp. Med. (2004) [Pubmed]
  5. Cutting edge: CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion. Aichele, P., Unsoeld, H., Koschella, M., Schweier, O., Kalinke, U., Vucikuja, S. J. Immunol. (2006) [Pubmed]
  6. Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. Auerbuch, V., Brockstedt, D.G., Meyer-Morse, N., O'Riordan, M., Portnoy, D.A. J. Exp. Med. (2004) [Pubmed]
  7. Interferons regulate the phenotype of wild-type and mutant herpes simplex viruses in vivo. Leib, D.A., Harrison, T.E., Laslo, K.M., Machalek, M.A., Moorman, N.J., Virgin, H.W. J. Exp. Med. (1999) [Pubmed]
  8. Requirement of type I interferon signaling for arthritis triggered by double-stranded RNA. Magnusson, M., Zare, F., Tarkowski, A. Arthritis Rheum. (2006) [Pubmed]
  9. Type I IFN receptor signals directly stimulate local B cells early following influenza virus infection. Coro, E.S., Chang, W.L., Baumgarth, N. J. Immunol. (2006) [Pubmed]
  10. N-glycosylation of murine IFN-beta in a putative receptor-binding region. Sommereyns, C., Michiels, T. J. Interferon Cytokine Res. (2006) [Pubmed]
  11. Endogenous IFN-alpha beta suppresses colony-stimulating factor (CSF)-1-stimulated macrophage DNA synthesis and mediates inhibitory effects of lipopolysaccharide and TNF-alpha. Hamilton, J.A., Whitty, G.A., Kola, I., Hertzog, P.J. J. Immunol. (1996) [Pubmed]
  12. Type I interferon inhibits antibody responses induced by a chimpanzee adenovirus vector. Hensley, S.E., Cun, A.S., Giles-Davis, W., Li, Y., Xiang, Z., Lasaro, M.O., Williams, B.R., Silverman, R.H., Ertl, H.C. Mol. Ther. (2007) [Pubmed]
  13. A novel gene of beta chain of the IFN-gamma receptor of Huiyang chicken: cloning, distribution, and CD assay. Han, C.L., Zhang, W., Dong, H.T., Han, X., Wang, M. J. Interferon Cytokine Res. (2006) [Pubmed]
  14. Interferon-dependent activation of the serine kinase PI 3'-kinase requires engagement of the IRS pathway but not the Stat pathway. Uddin, S., Majchrzak, B., Wang, P.C., Modi, S., Khan, M.K., Fish, E.N., Platanias, L.C. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  15. Type I IFN negatively regulates CD8+ T cell responses through IL-10-producing CD4+ T regulatory 1 cells. Dikopoulos, N., Bertoletti, A., Kröger, A., Hauser, H., Schirmbeck, R., Reimann, J. J. Immunol. (2005) [Pubmed]
  16. Structure of the murine interferon alpha/beta receptor-encoding gene: high-frequency rearrangements in the interferon-resistant L1210 cell line. Lutfalla, G., Uzé, G. Gene (1994) [Pubmed]
  17. Production of type I IFN sensitizes macrophages to cell death induced by Listeria monocytogenes. Stockinger, S., Materna, T., Stoiber, D., Bayr, L., Steinborn, R., Kolbe, T., Unger, H., Chakraborty, T., Levy, D.E., Müller, M., Decker, T. J. Immunol. (2002) [Pubmed]
  18. Type I interferons trigger systemic, partial lymphocyte activation in response to viral infection. Alsharifi, M., Lobigs, M., Regner, M., Lee, E., Koskinen, A., Müllbacher, A. J. Immunol. (2005) [Pubmed]
  19. The soluble murine type I interferon receptor Ifnar-2 is present in serum, is independently regulated, and has both agonistic and antagonistic properties. Hardy, M.P., Owczarek, C.M., Trajanovska, S., Liu, X., Kola, I., Hertzog, P.J. Blood (2001) [Pubmed]
  20. The immune response modifier imiquimod requires STAT-1 for induction of interferon, interferon-stimulated genes, and interleukin-6. Bottrel, R.L., Yang, Y.L., Levy, D.E., Tomai, M., Reis, L.F. Antimicrob. Agents Chemother. (1999) [Pubmed]
  21. Type I interferons potently suppress gene expression following gene delivery using liposome(-)DNA complexes. Sellins, K., Fradkin, L., Liggitt, D., Dow, S. Mol. Ther. (2005) [Pubmed]
  22. Type I interferons and IRF-1 play a critical role in the control of a gammaherpesvirus infection. Dutia, B.M., Allen, D.J., Dyson, H., Nash, A.A. Virology (1999) [Pubmed]
  23. Replication of bovine respiratory syncytial virus in murine cells depends on type I interferon-receptor functionality. Riffault, S., Dubuquoy, C., Castagné, N., Baranowski, E., Charley, B., Eléouët, J.F. J. Gen. Virol. (2006) [Pubmed]
  24. Type I interferons are essential mediators of apoptotic death in virally infected cells. Tanaka, N., Sato, M., Lamphier, M.S., Nozawa, H., Oda, E., Noguchi, S., Schreiber, R.D., Tsujimoto, Y., Taniguchi, T. Genes Cells (1998) [Pubmed]
  25. Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo. Yano, H., Ogasawara, S., Momosaki, S., Akiba, J., Kojiro, S., Fukahori, S., Ishizaki, H., Kuratomi, K., Basaki, Y., Oie, S., Kuwano, M., Kojiro, M. Liver Int. (2006) [Pubmed]
 
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