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Nature Immunology 9, 542–550 (1 May 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 An , Jin Hou , Jun Zhou , Wei Zhao , Hongmei Xu , Yuejuan Zheng , Yizhi Yu , Shuxun Liu & Xuetao Cao

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-κB 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.