Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 46, Issue -, Pages 44-49Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2014.12.007
Keywords
Multiple sclerosis; Experimental autoimmune encephalomyelitis; TGF-beta 1; TGF-beta 3; T cell encephalitogenicity; Th17 cells; IL-23R; GM-CSF
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Funding
- National Institutes of Health [R01-NS067441 - AELR]
- Clinical Translational Science Award [TL1TR000091-05]
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The phenotype of the CD4(+) T cells that mediate the CNS pathology in multiple sclerosis is still unclear, and yet a vital question for developing therapies. One of the conundrums is the role of TGF-beta in the development of encephalitogenic Th17 cells. In the present study, TGF-beta 1 and TGF-beta 3 were directly compared in their capacity to promote the differentiation of myelin-specific Th17 cells that could induce experimental autoimmune encephalomyelitis (EAE). Myelin-specific CD4(+) T cell receptor transgenic cells differentiated with antigen in the presence of IL-6+TGF-beta 1 or IL-6+TGF-beta 3 generated T cells that produced robust amounts of IL-17, but were incapable of inducing EAE when transferred into mice. Further analysis of these non-encephalitogenic Th17 cells found that they expressed lower amounts of GM-CSF or IL-23R, both molecules necessary for encephalitogenicity. Thus, TGF-beta, irrespective of isoform, negatively regulates the differentiation of encephalitogenic Th17 cells. (C) 2014 Elsevier Inc. All rights reserved.
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