Research ArticleInflammation

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

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Science Signaling  03 Mar 2015:
Vol. 8, Issue 366, pp. ra24
DOI: 10.1126/scisignal.aaa2147

Interpreting immune signals in the CNS

In mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, T helper 17 (TH17) cells, which secrete the proinflammatory cytokine interleukin-17 (IL-17), are among the first immune cells to infiltrate the central nervous system (CNS), and they play a pathogenic role in the disease (see the Focus by Gaffen and McGeachy). Huang et al. found that the mitogen-activated protein kinase p38α was critical in mediating IL-17–dependent signaling in mice with EAE. Loss of p38α in CNS cells such as astrocytes inhibited IL-17–dependent gene expression, suppressed the further recruitment of immune cells, and decreased disease severity in mice. Conversely, mice deficient in a phosphatase that inhibits p38α showed exacerbated disease symptoms, suggesting that this signaling pathway might be targeted to treat MS.

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