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

Nature immunology | Sep 20, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19668221

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 RIS Download

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

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Associated grants

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

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