期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 44, 期 10, 页码 2979-2989出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201344140
关键词
Rheumatoid arthritis; Regulatory T cells; FOXP3; Th17; CD39
类别
资金
- Swedish Association against Rheumatism
- King Gustaf V 80-year Foundation
- TREG CENTER consortia
- EU-FP7 project Masterswitch [HEALTHF-2-2008-223404]
- IMI-JU [115142-2]
- Swedish Foundation for Strategic Research [305549-2]
- Initial Training Networks 7th framework program Osteoimmune [289150]
- Swedish Research Council
Treg cells are important for the maintenance of self-tolerance and are implicated in autoimmunity. Despite enrichment of Treg cells in joints of rheumatoid arthritis (RA) patients, local inflammation persists. As expression of the ATP-hydrolyzing enzymes CD39 and CD73 and the resulting anti-inflammatory adenosine production have been implicated as an important mechanism of suppression, we characterized FOXP3(+) Treg cells in blood and synovial fluid samples of RA patients in the context of CD39 and CD73 expression. Synovial FOXP3(+) Treg cells displayed high expression levels of rate-limiting CD39, whereas CD73 was diminished. FOXP3(+) CD39(+) Treg cells were also abundant in synovial tissue. Furthermore, FOXP3(+) CD39(+) Treg cells did not secrete the proinflammatory cytokines IFN-gamma and TNF after in vitro stimulation in contrast to FOXP3(+) CD39(-) T cells. FOXP3(+) CD39(+) Treg cells could be isolated by CD39 and CD25 coexpression, displayed a demethylated Treg-specific demethylated region and coculture assays confirmed that CD25(+) CD39(+) T cells have suppressive capacity, while their CD39(-) counterparts do not. Overall, our data show that FOXP3(+) CD39(+) Treg cells are enriched at the site of inflammation, do not produce proinflammatory cytokines, and are good suppressors of many effector T-cell functions including production of IFN-gamma, TNF, and IL-17F but do not limit IL-17A secretion.
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