Article abstract
Nature Immunology 9, 542 - 550 (2008)
Published online: 6 April 2008 | doi:10.1038/ni.1604
Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1
Huazhang An1, Jin Hou1, Jun Zhou1, Wei Zhao1, Hongmei Xu1, Yuejuan Zheng1, Yizhi Yu1, Shuxun Liu1 & Xuetao Cao1
Abstract
Unbalanced production of proinflammatory cytokines and type I interferons in immune responses may lead to immunopathology; thus, the mechanisms that ensure the beneficial production of proinflammatory cytokines and type I interferons are of particular importance. Here we demonstrate that the phosphatase SHP-1 negatively regulated Toll-like receptor–mediated production of proinflammatory cytokines by inhibiting activation of the transcription factor NF-
B and mitogen-activated protein kinase. Simultaneously, SHP-1 increased the production of type I interferon mediated by Toll-like receptors and the helicase RIG-I by directly binding to and inhibiting activation of the kinase IRAK1. Our data demonstrate that SHP-1 contributes to immune homeostasis by balancing the production of proinflammatory cytokines and type I interferons in the innate immune response.
- Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
Correspondence to: Xuetao Cao1 e-mail: caoxt@public3.sta.net.cn
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