Disease relevance of Ifnar1

• 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 [1].
• 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 [2].
• Although the inflammation is transient in wild-type animals and resolves upon Pneumocystis clearance, it is more severe and persists through day 35 postinfection in IFNAR KO mice, leading to fibrosis [3].
• PVR-transgenic/Ifnar knockout mice showed increased susceptibility to poliovirus [4].
• To investigate whether the presence of the wild-type NSs gene correlated with inhibition of IFN-alpha/beta production, we infected susceptible IFNAR(-/-) mice with S gene reassortant viruses [5].
• Similar to its proposed role in human SLE, signaling via the IFNAR is central to the pathogenesis of autoantibodies and glomerulonephritis in TMPD-induced lupus [6].

High impact information on Ifnar1

• Unlike other dendritic cell (DC) subsets, FACS((R))-sorted CD11c(int)CD11b(-)GR-1(+) DCs show high IFN-alpha expression, irrespective of whether they were isolated from VSV-infected IFNAR-competent or -deficient mice [1].
• Furthermore, intraarticular deposition of IFNalpha induced arthritis in PKR(-/-) and control mice, whereas IFNAR(-/-) mice were protected [7].
• CD25(+)FoxP3(+) T(R) cells down-modulate vaccine-primed CD8(+) T cell responses in normal, IFNAR(-/-), or IFN-beta(-/-) mice to a comparable extent [8].
• However, in both CD4 competent, wild-type and IFN-alpha receptor (IFNAR) KO mice, Pneumocystis infection leads to an eosinophilic granulocyte influx with bronchial epithelial changes as seen in asthma [3].
• One of these proteins, referred to as the human interferon alpha receptor (IFNAR), has been shown to be involved in interferon signal transduction, but it does not bind IFN with high affinity [9].

Chemical compound and disease context of Ifnar1

• 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) [10].

Biological context of Ifnar1

• We also present a revised Il10r2 cDNA sequence with a total of 100 bp of additional nucleotide sequence in the 5' and 3' untranslated regions, and report the first extensive profiles of Il10r2 and Ifnar1 mRNA developmental stage and adult tissue expression [11].
• In this study we show, using a panel of CHO-human chromosome 21 hybrid cell lines which all express IFNAR, that only those containing the region 21q22.2 to 21q22.3 transduce signals for IFN responses [12].
• The increased antibody response in IFNAR(-/-) mice vaccinated with the AdC68 vector was mainly due to the generation of IgG1 antibodies that were not elicited in wild-type mice [13].
• The induction of IgG1 antibodies correlated with an increase in transgene product expression in IFNAR(-/-) mice and was not associated with an increase in T helper 2 responses [13].
• WNV infection of wt MEFs resulted in a greater up-regulation of MHC-I than did infection of IFNAR(-/-) MEFs because of the action of endogenous type 1 IFN production [14].

Anatomical context of Ifnar1

• METHODS: IFNalpha and different forms of RNA were injected into the knee joints of wild-type mice, mice lacking the type I interferon receptor (IFNAR(-/-)), and mice deficient in dsRNA-dependent protein kinase (PKR(-/-)) [7].
• In addition, the percentage of CD8(+) and B lymph-node cells expressing CD69 after PRV-gC DNA vaccination was lower in IFNAR K/O than in WT mice [10].
• With all three tumor cell lines, tumor development and ensuing mortality were enhanced in the IFNAR KO animals [15].
• The human interferon alpha-receptor (IFNAR gene product or IFN alpha R protein) was expressed in hamster CHO cells and in mouse A9 cells [16].
• We report that bone marrow-derived macrophages (BMM) lacking a component of the type I interferon receptor (IFNAR-1) do not express cyclin D2 mRNA or protein in response to LPS stimulation (0.01-1 microg/ml for 7-30 h) [17].

Associations of Ifnar1 with chemical compounds

• Earlier results from our laboratory suggested that an association of IFNAR-1 with membrane Galalpha1-4Gal-containing glycolipids facilitates receptor-mediated signaling [18].

Physical interactions of Ifnar1

• 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 Ifnar1

• Following footpad infection, both IFNAR-1-/- and IRF-2-/- mice were more susceptible than control mice to VEE [20].
• In this report, we show that MP12 and clone 13, two attenuated RVFV strains with mutations in the NSs gene, were highly virulent in IFNAR(-/-) mice lacking the alpha/beta interferon (IFN-alpha/beta) receptor but remained attenuated in IFN-gamma receptor-deficient mice [5].
• GART, SON, IFNAR, and CRF2-4 genes cluster on human chromosome 21 and mouse chromosome 16 [21].

Analytical, diagnostic and therapeutic context of Ifnar1

• Twice as many CD8(+) T cells specific for different class I-restricted epitopes develop in IFNAR(-/-) or IFN-beta(-/-) mice than in normal animals after peptide- or DNA-based vaccination [8].
• We have established a new animal model, genetically targeted mice lacking a functional interferon type I receptor (IFNAR-1) [22].

References