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Signaling by the Phosphatase MKP-1 in Dendritic Cells Imprints Distinct Effector and Regulatory T Cell Fates by Gonghua Huang; Yanyan Wang; Lewis Z. Shi; Thirumala-Devi Kanneganti; Hongbo Chi is a Immunology and Microbiology article available to read on EtoBox.

What is Signaling by the Phosphatase MKP-1 in Dendritic Cells Imprints Distinct Effector and Regulatory T Cell Fates about?

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-b2 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.

Who reads Signaling by the Phosphatase MKP-1 in Dendritic Cells Imprints Distinct Effector and Regulatory T Cell Fates?

Author

Gonghua Huang; Yanyan Wang; Lewis Z. Shi; Thirumala-Devi Kanneganti; Hongbo Chi

Publisher

Elsevier Science; Elsevier ; Cell Press; Elsevier BV (ISSN 1074-7613)

Published

2011

Language

EN

Field

Immunology and Microbiology (Life Sciences)