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

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.

Pubmed ID: 19668221


  • Kawagoe T
  • Takeuchi O
  • Takabatake Y
  • Kato H
  • Isaka Y
  • Tsujimura T
  • Akira S


Nature immunology

Publication Data

September 20, 2009

Associated Grants

  • Agency: NIAID NIH HHS, Id: P01 AI070167
  • Agency: NIAID NIH HHS, Id: P01 AI070167-030003

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, CD40
  • Autoimmune Diseases
  • Autoimmunity
  • Female
  • Glomerulonephritis
  • Intestines
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Differentiation Factor 88
  • Receptors, Antigen, B-Cell
  • Signal Transduction
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptors
  • Ubiquitin