• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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