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- Title
TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis.
- Authors
Kawagoe, Tatsukata; Takeuchi, Osamu; Takabatake, Yoshitsugu; Kato, Hiroki; Isaka, Yoshitaka; Tsujimura, Tohru; Akira, Shizuo
- Abstract
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-κB. 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.
- Subjects
KIDNEY diseases; IMMUNE response; ANTIVIRAL agents; ANTINEOPLASTIC agents; KILLER cells
- Publication
Nature Immunology, 2009, Vol 10, Issue 9, p965
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1771