title: Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis.
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.
authors.affiliation: Department of Medicine, Immunobiology Program, University of Vermont, Burlington, VT, USA.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Noubade
authors.forename: Dimitry N
authors.initials: DN
authors.lastname: Krementsov
authors.forename: Roxana
authors.initials: R
authors.lastname: Del Rio
authors.forename: Tina
authors.initials: T
authors.lastname: Thornton
authors.forename: Viswas
authors.initials: V
authors.lastname: Nagaleekar
authors.forename: Naresha
authors.initials: N
authors.lastname: Saligrama
authors.forename: Anthony
authors.initials: A
authors.lastname: Spitzack
authors.forename: Karen
authors.initials: K
authors.lastname: Spach
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Sabio
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rincon
authors.forename: Cory
authors.initials: C
authors.lastname: Teuscher
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015551:Autoimmunity; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D002908:Chronic Disease; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D039561:Eukaryotic Initiation Factor-4E; D020381:Interleukin-17; D048051:p38 Mitogen-Activated Protein Kinases