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

Youcun Qian, Caini Liu, Justin Hartupee, Cengiz Zubeyir Altuntas, Muhammet Fatih Gulen, Daniel Jane-Wit, Jianhua Xiao, Yi Lu, Natalia Giltiay, Jinbo Liu, Tomasz Kordula, Qi Wei Zhang, Bruce Vallance, Shadi Swaidani, Mark Aronica, Vincent K. Tuohy, Thomas Hamilton, Xiaoxia Li

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361 Scopus citations

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-κB. 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.

Original languageEnglish
Pages (from-to)247-256
Number of pages10
JournalNature immunology
Volume8
Issue number3
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

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    Qian, Y., Liu, C., Hartupee, J., Altuntas, C. Z., Gulen, M. F., Jane-Wit, D., Xiao, J., Lu, Y., Giltiay, N., Liu, J., Kordula, T., Zhang, Q. W., Vallance, B., Swaidani, S., Aronica, M., Tuohy, V. K., Hamilton, T., & Li, X. (2007). The adaptor Act1 is required for interleukin 17 - Dependent signaling associated with autoimmune and inflammatory disease. Nature immunology, 8(3), 247-256. https://doi.org/10.1038/ni1439