Journal
JOURNAL OF AUTOIMMUNITY
Volume 59, Issue -, Pages 38-42Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2015.02.001
Keywords
IL-17; T cells; Macrophages; Cytokines
Categories
Funding
- National Institutes of Health [R01DK096138, R56AI044880]
- National Multiple Sclerosis Society [NMSSRG2571, NMSSRG4374]
- Brigham and Women's Hospital
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Genetic variants in il2 and il2ra have been associated with autoimmune disease susceptibility in both genome-wide association studies (GWAS) in humans and in genetic linkage studies in experimental models of autoimmunity. Specifically, genetic variants resulting in a low IL-2 phenotype are susceptibility alleles while variants resulting in a high IL-2 phenotype are resistance alleles. The association of high IL-2 phenotypes with resistance has been attributed primarily to the T cell intrinsic promotion of regulatory T cell development, maintenance, and function; however, IL-2 can also act T cell intrinsically to dampen differentiation of pathogenic IL-17-producing Th17 cells. Here, we have uncovered a novel T cell extrinsic mechanism whereby IL-2 promotes both IFN-gamma and IL-27 production from tissue resident macrophages which in turn dampen the differentiation of pathogenic Th17 cells. (C) 2015 Elsevier Ltd. All rights reserved.
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