期刊
JOURNAL OF IMMUNOLOGY
卷 189, 期 9, 页码 4237-4246出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1201476
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资金
- intramural research program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health
- National Research Council, National Academy of Sciences
- Grants-in-Aid for Scientific Research [22570006, 22510219] Funding Source: KAKEN
IL-15 is an important IL-2-related cytokine whose role in Th17 cell biology has not been fully elucidated. In this study, we show that exogenous IL-15 decreased IL-17A production in Th17 cultures. Neutralization of IL-15 using an Ab led to increases in IL17A production in Th17 cultures. Both Il15(-/-) and Il15r(-/-) T cell cultures displayed higher frequency of IL-17A producers and higher amounts of IL-17A in the supernatants compared with those of wild-type (WT) cells in vitro. IL-15 down-modulated IL-17A production independently of retinoic acid-related orphan receptor-gamma t, Foxp3, and IFN-gamma expression. Both Th17 cells and APCs produced IL-15, which induced binding of STAT5, an apparent repressor to the Il17 locus in CD4 T cells. Also, in a model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), Il15(-/-) mice displayed exacerbated inflammation-correlating with increased IL-17A production by their CD4(+) T cells-compared with WT controls. Exogenous IL-15 administration and IL-17A neutralization reduced the severity of EAE in Il15(-/-) mice. Taken together, these data indicate that IL-15 has a negative regulatory role in fine-tuning of IL-17A production and Th17-mediated inflammation. The Journal of Immunology, 2012, 189: 4237-4246.
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