title: Signaling by the phosphatase MKP-1 in dendritic cells imprints distinct effector and regulatory T cell fates.
abstract: Naive T cells respond to antigens by differentiating into effector and regulatory lineages. Whereas the roles of T cell-intrinsic pathways have been extensively studied, how T cell lineage choices are controlled by innate immune signals remains elusive. Here we report that dendritic cell (DC)-expressed phosphatase MKP-1, a negative regulator of the MAP kinases, programmed reciprocal T helper 1 (Th1) and Th17 cell differentiation by modulating IL-12-STAT4 and IL-6-STAT3 axes and cytokine receptor expression at the DC-T cell interface. MKP-1 was regulated by innate recognition signals and its deficiency disrupted antimicrobial responses and promoted T cell-mediated inflammation. Moreover, MKP-1 inhibited induction of regulatory T cells by downregulating TGF-β2 production from DCs. Our findings identify a regulatory circuit linking MKP-1 signaling in DCs, production of polarizing cytokines, and integration of DC-derived signals in responding T cells, that bridges innate and adaptive immunity to coordinate protective immunity and immunopathology.
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Gonghua
authors: G
authors: Huang
authors: Yanyan
authors: Y
authors: Wang
authors: Lewis Z
authors: LZ
authors: Shi
authors: Thirumala-Devi
authors: TD
authors: Kanneganti
authors: Hongbo
authors: H
authors: Chi
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D002177:Candidiasis / Q000276:immunology*; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D007113:Immunity, Innate; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D054638:Dual Specificity Phosphatase 1