| First Author | Huang G | Year | 2011 |
| Journal | Immunity | Volume | 35 |
| Issue | 1 | Pages | 45-58 |
| PubMed ID | 21723158 | Mgi Jnum | J:174378 |
| Mgi Id | MGI:5085948 | Doi | 10.1016/j.immuni.2011.05.014 |
| Citation | Huang G, et al. (2011) Signaling by the Phosphatase MKP-1 in Dendritic Cells Imprints Distinct Effector and Regulatory T Cell Fates. Immunity 35(1):45-58 |
| abstractText | 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-beta2 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. |
