Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis

Rajkumar Noubade, Dimitry N. Krementsov, Roxana Del Rio, Tina Thornton, Viswas Nagaleekar, Naresha Saligrama, Anthony Spitzack, Karen Spach, Guadalupe Sabio, Roger J. Davis, Mercedes Rincon, Cory Teuscher

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Although several transcription factors have been shown to be critical for the induction and maintenance of IL-17 expression by CD4 Th cells, less is known about the role of nontranscriptional mechanisms. Here we show that the p38 MAPK signaling pathway is essential for in vitro and in vivo IL-17 production by regulating IL-17 synthesis in CD4 T cells through the activation of the eukaryotic translation initiation factor 4E/MAPK-interacting kinase (eIF-4E/MNK) pathway. We also show that p38 MAPK activation is required for the development and progression of both chronic and relapsing-remitting forms of experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis. Furthermore, we show that regulation of p38 MAPK activity specifically in T cells is sufficient to modulate EAE severity. Thus, mechanisms other than the regulation of gene expression also contribute to Th17 cell effector functions and, potentially, to the pathogenesis of other Th17 cell-mediated diseases.

Original languageEnglish
Pages (from-to)3290-3300
Number of pages11
JournalBlood
Volume118
Issue number12
DOIs
StatePublished - Sep 22 2011

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