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Control of IL-17 receptor signaling and tissue inflammation by the p38?-MKP-1 signaling axis in a mouse model of multiple sclerosis.


ABSTRACT: T helper 17 (T(H)17) cells, a subset of CD4+ T cells that secrete the proinflammatory cytokine interleukin-17 (IL-17), play a key pathogenic role in autoimmune diseases. Through inducible and tissue-specific deletion systems, we described the time- and tissue-specific roles of the mitogen-activated protein kinase (MAPK) p38? in mediating T(H)17 cell-induced tissue inflammation. Inducible deletion of Mapk14 (which encodes p38?) after the onset of experimental autoimmune encephalomyelitis (EAE), a murine model for human multiple sclerosis, protected mice from inflammation. Furthermore, the severity of EAE was markedly reduced in mice with specific loss of p38? in neuroectoderm-derived cells, including astrocytes, an effect that was associated with defective production of chemokines and decreased infiltration of the target tissue by immune cells. p38? linked IL-17 receptor (IL-17R) signaling to the expression of genes encoding proinflammatory chemokines and cytokines. Mice that lacked MAPK phosphatase 1 (MKP-1), an inhibitor of p38?, had exacerbated EAE and enhanced expression of IL-17R-dependent genes. Our results suggest that the p38?-MKP-1 signaling axis links IL-17R signaling in tissue-resident cells to autoimmune inflammation dependent on infiltrating T(H)17 cells.

SUBMITTER: Huang G 

PROVIDER: S-EPMC4640462 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Control of IL-17 receptor signaling and tissue inflammation by the p38α-MKP-1 signaling axis in a mouse model of multiple sclerosis.

Huang Gonghua G   Wang Yanyan Y   Vogel Peter P   Chi Hongbo H  

Science signaling 20150303 366


T helper 17 (T(H)17) cells, a subset of CD4+ T cells that secrete the proinflammatory cytokine interleukin-17 (IL-17), play a key pathogenic role in autoimmune diseases. Through inducible and tissue-specific deletion systems, we described the time- and tissue-specific roles of the mitogen-activated protein kinase (MAPK) p38α in mediating T(H)17 cell-induced tissue inflammation. Inducible deletion of Mapk14 (which encodes p38α) after the onset of experimental autoimmune encephalomyelitis (EAE), a  ...[more]

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