Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1.
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-kappaB 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.
An
Huazhang
H
Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
Hou
Jin
J
Zhou
Jun
J
Zhao
Wei
W
Xu
Hongmei
H
Zheng
Yuejuan
Y
Yu
Yizhi
Y
Liu
Shuxun
S
Cao
Xuetao
X
D000818:Animals; D020134:Catalytic Domain / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D006706:Homeostasis / Q000276:immunology; D007113:Immunity, Innate; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007370:Interferon Type I / Q000096:biosynthesis*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D017737:Macrophages, Peritoneal; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D000097905:Roundabout Proteins
D016207:Cytokines; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I; D053592:Interleukin-1 Receptor-Associated Kinases; D008565:Membrane Proteins; D020929:Mitogen-Activated Protein Kinase Kinases; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C507769:Irak1 protein, mouse