The kinase TBK1 controls IgA class switching by negatively regulating noncanonical NF-κB signaling

被引：116

作者：

Jin, Jin ^{[1
]}

Xiao, Yichuan ^{[1
]}

Chang, Jae-Hoon ^{[1
]}

Yu, Jiayi ^{[1
]}

Hu, Hongbo ^{[1
]}

Starr, Robyn ^{[2
]}

Brittain, George C. ^{[1
]}

Chang, Mikyoung ^{[1
]}

Cheng, Xuhong ^{[1
]}

Sun, Shao-Cong ^{[1
,3
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[2] St Vincents Inst, Fitzroy, Vic, Australia

[3] Univ Texas Grad Sch Biomed Sci Houston, Houston, TX USA

来源：

NATURE IMMUNOLOGY | 2012年 / 13卷 / 11期

基金：

美国国家卫生研究院;

关键词：

ANTIVIRAL RESPONSE; INNATE IMMUNITY; CROSS-TALK; RECEPTOR; ACTIVATION; EXPRESSION; DEFICIENT; FAMILY; CELLS; MOUSE;

D O I：

10.1038/ni.2423

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Immunoglobulin class switching is crucial for the generation of antibody diversity in humoral immunity and, when deregulated, also has severe pathological consequences. How the magnitude of immunoglobulin isotype switching is controlled is still poorly understood. Here we identify the kinase TBK1 as a pivotal negative regulator of class switching to the immunoglobulin A (IgA) isotype. B cell specific ablation of TBK1 in mice resulted in uncontrolled production of IgA and the development of nephropathy-like disease signs. TBK1 negatively regulated IgA class switching by attenuating noncanonical signaling via the transcription factor NF-kappa B, an action that involved TBK1-mediated phosphorylation and subsequent degradation of the NF-kappa B-inducing kinase NIK. Our findings establish TBK1 as a pivotal negative regulator of the noncanonical NF-kappa B pathway and identify a unique mechanism that controls IgA production.

引用

页码：1101 / 1109

页数：9