| First Author | Kawagoe T | Year | 2009 |
| Journal | Nat Immunol | Volume | 10 |
| Issue | 9 | Pages | 965-72 |
| PubMed ID | 19668221 | Mgi Jnum | J:151757 |
| Mgi Id | MGI:4355244 | Doi | 10.1038/ni.1771 |
| Citation | Kawagoe T, et al. (2009) TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis. Nat Immunol 10(9):965-72 |
| abstractText | 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-kappaB. 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. |
