Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity

被引：85

作者：

Tun-Kyi, Adrian ^{[1
]}

Finn, Greg ^{[1
]}

Greenwood, Alex ^{[2
]}

Nowak, Michael ^{[1
]}

Lee, Tae Ho ^{[1
]}

Asara, John M. ^{[1
]}

Tsokos, George C. ^{[1
]}

Fitzgerald, Kate ^{[3
]}

Israel, Elliot ^{[4
]}

Li, Xiaoxia ^{[5
]}

Exley, Mark ^{[1
]}

Nicholson, Linda K. ^{[2
]}

Lu, Kun Ping ^{[1
]}

机构：

[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA

[2] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA

[3] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA

[4] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[5] Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 08期

基金：

美国国家卫生研究院;

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; PATTERN-RECOGNITION RECEPTORS; MURINE CYTOMEGALOVIRUS; INTERLEUKIN-1; RECEPTOR; ADAPTIVE IMMUNITY; ALPHA INDUCTION; VIRAL-INFECTION; DENDRITIC CELLS; RESPONSES; KINASE;

D O I：

10.1038/ni.2069

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Toll-like receptors (TLRs) shape innate and adaptive immunity to microorganisms. The enzyme IRAK1 transduces signals from TLRs, but mechanisms for its activation and regulation remain unknown. We found here that TLR7 and TLR9 activated the isomerase Pin1, which then bound to IRAK1; this resulted in activation of IRAK1 and facilitated its release from the receptor complex to activate the transcription factor IRF7 and induce type I interferons. Consequently, Pin1-deficient cells and mice failed to mount TLR-mediated, interferon-dependent innate and adaptive immune responses. Given the critical role of aberrant activation of IRAK1 and type I interferons in various immune diseases, controlling IRAK1 activation via inhibition of Pin1 may represent a useful therapeutic approach.

引用

页码：733 / U142

页数：10

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