title: Surface expression of CD39 identifies an enriched Treg-cell subset in the rheumatic joint, which does not suppress IL-17A secretion.
abstract: 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-γ 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-γ, TNF, and IL-17F but do not limit IL-17A secretion.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Herrath
authors.forename: Karine
authors.initials: K
authors.lastname: Chemin
authors.forename: Inka
authors.initials: I
authors.lastname: Albrecht
authors.forename: Anca I
authors.initials: AI
authors.lastname: Catrina
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D001081:Apyrase / Q000096:biosynthesis* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D013582:Synovial Fluid / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C508717:IL17A protein, human; D020381:Interleukin-17; D001081:Apyrase; C067869:CD39 antigen
keywords: CD39; FOXP3; Regulatory T cells; Rheumatoid arthritis; Th17