Structural basis of a unique interferon-β signaling axis mediated via the receptor IFNAR1

被引：211
作者：
de Weerd, Nicole A. [1 ,2 ]
Vivian, Julian P. [3 ]
Nguyen, Thao K. [1 ,2 ,3 ]
Mangan, Niamh E. [1 ]
Gould, Jodee A. [1 ,2 ]
Braniff, Susie-Jane [1 ]
Zaker-Tabrizi, Leyla [1 ]
Fung, Ka Yee [1 ]
Forster, Samuel C. [1 ,2 ]
Beddoe, Travis [3 ]
Reid, Hugh H. [3 ]
Rossjohn, Jamie [2 ,3 ,4 ]
Hertzog, Paul J. [1 ,2 ]
机构：
[1] Monash Univ, Monash Inst Med Res, Ctr Innate Immun & Infect Dis, Clayton, Vic, Australia
[2] Monash Univ, Australian Res Council Ctr Excellence Struct & Fu, Clayton, Vic, Australia
[3] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic, Australia
[4] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales
来源：
NATURE IMMUNOLOGY | 2013年 / 14卷 / 09期
基金：
澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词：
I INTERFERONS; ALPHA; LIPOPOLYSACCHARIDE; INDUCTION; RESPONSES; SUBUNIT; ACTIVATION; REFINEMENT; SUPPRESSOR;
D O I：
10.1038/ni.2667
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Type I interferons are important in regulating immune responses to pathogens and tumors. All interferons are considered to signal via the heterodimeric IFNAR1-IFNAR2 complex, yet some subtypes such as interferon-beta ( IFN-beta) can exhibit distinct functional properties, although the molecular basis of this is unclear. Here we demonstrate IFN-beta can uniquely and specifically ligate to IFNAR1 in an IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN-beta interaction. The IFNAR1-IFN-beta complex transduced signals that modulated expression of a distinct set of genes independently of Jak-STAT pathways. Lipopolysaccharide-induced sepsis was ameliorated in Ifnar1(-/-) mice but not Ifnar2(-/-) mice, suggesting that IFNAR1-IFN-beta signaling is pathologically relevant. Thus, we provide a molecular basis for understanding specific functions of IFN-beta.
引用
收藏
页码：901 / +
页数：9
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