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The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease.

T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-kappaB. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease.

Pubmed ID: 17277779


  • Qian Y
  • Liu C
  • Hartupee J
  • Altuntas CZ
  • Gulen MF
  • Jane-Wit D
  • Xiao J
  • Lu Y
  • Giltiay N
  • Liu J
  • Kordula T
  • Zhang QW
  • Vallance B
  • Swaidani S
  • Aronica M
  • Tuohy VK
  • Hamilton T
  • Li X


Nature immunology

Publication Data

March 16, 2007

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI 065470

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Adoptive Transfer
  • Animals
  • Antigens, CD40
  • Autoimmune Diseases
  • Autoimmunity
  • B-Cell Activation Factor Receptor
  • Colitis
  • Encephalomyelitis, Autoimmune, Experimental
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Inflammation
  • Interleukin-17
  • Mice
  • Receptors, Interleukin-17
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • T-Lymphocytes
  • Transfection
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins