TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis

被引：140

作者：

Kawagoe, Tatsukata ^{[1
,2
]}

Takeuchi, Osamu ^{[1
,2
]}

Takabatake, Yoshitsugu ^{[3
]}

Kato, Hiroki ^{[1
,2
]}

Isaka, Yoshitaka ^{[4
]}

Tsujimura, Tohru ^{[5
]}

Akira, Shizuo ^{[1
,2
]}

机构：

[1] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Host Def Lab, Osaka, Japan

[2] Osaka Univ, Res Inst Microbial Dis, Osaka, Japan

[3] Osaka Univ, Grad Sch Med, Dept Nephrol, Osaka, Japan

[4] Osaka Univ, Grad Sch Med, Dept Adv Technol Transplantat, Osaka, Japan

[5] Hyogo Coll Med, Dept Pathol, Nishinomiya, Hyogo, Japan

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 09期

基金：

美国国家卫生研究院;

关键词：

NF-KAPPA-B; INTERFERON ANTIVIRAL RESPONSE; DEUBIQUITINATING ENZYME; UBIQUITIN LIGASE; ACTIVATION; KINASE; INNATE; RECOGNITION; PROTEIN; FAMILY;

D O I：

10.1038/ni.1771

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The intensity and duration of immune responses are controlled by many proteins that modulate Toll-like receptor (TLR) signaling. TANK has been linked to positive regulation of the transcription factors IRF3 and NF-kappa B. Here we demonstrate that TANK is not involved in interferon responses and is a negative regulator of proinflammatory cytokine production induced by TLR signaling. TLR-induced polyubiquitination of the ubiquitin ligase TRAF6 was upregulated in Tank(-/-) macrophages. Notably, Tank(-/-) mice spontaneously developed fatal glomerulonephritis owing to deposition of immune complexes. Autoantibody production in Tank(-/-) mice was abrogated by antibiotic treatment or the absence of interleukin 6 (IL-6) or the adaptor MyD88. Our results demonstrate that constitutive TLR signaling by intestinal commensal microflora is suppressed by TANK.

引用

页码：965 / U53

页数：9

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