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.
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
Nat. Immunol.
Date: Mar. 01, 2007
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