Article abstract
Nature Immunology 8, 247 - 256 (2007)
Published online: 4 February 2007 | doi:10.1038/ni1439
The adaptor Act1 is required for interleukin 17–dependent signaling associated with autoimmune and inflammatory disease
Youcun Qian1,6, Caini Liu1,6, Justin Hartupee1, Cengiz Zubeyir Altuntas1, Muhammet Fatih Gulen1, Daniel Jane-wit1, Jianhua Xiao1, Yi Lu1, Natalia Giltiay1, Jinbo Liu2, Tomasz Kordula3, Qi-Wei Zhang1, Bruce Vallance4, Shadi Swaidani5, Mark Aronica5, Vincent K Tuohy1, Thomas Hamilton1 & Xiaoxia Li1
Abstract
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-
B. 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.
- Department of Immunology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
- Department of Biochemistry, Virginia Commonwealth University Medical School, Richmond, Virginia 23298, USA.
- Division of Gastroenterology, University of British Columbia and BC Children's Hospital, Vancouver, British Columbia V6T 1Z4, Canada.
- Department of Pathobiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
- These authors contributed equally to this work.
Correspondence to: Xiaoxia Li1 e-mail: lix@ccf.org
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