CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL-17 in a STAT3-dependent manner.
Bottom Line: Importantly, we find that IL-17 production is STAT3 dependent, with Treg cells from patients with STAT3 mutations unable to make IL-17.Finally, we show that CD161(+) population III Treg cells accumulate in inflamed joints of patients with inflammatory arthritis and are the predominant IL-17-producing Treg-cell population at these sites.As IL-17 production from this Treg-cell subpopulation is not accompanied by a loss of regulatory function, in the context of cell therapy, exclusion of these cells from the cell product may not be necessary.
Affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London, UK. firstname.lastname@example.orgShow MeSH
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Mentions: Population III CD161+ Treg cells were further characterized to determine how similar they are to other Treg-cell subpopulations at baseline. We first examined expression of CD39, an ecto-enzyme involved in Treg-cell function , and HLA-DR, a marker of Treg cells with early contact-dependent suppression , by flow cytometry, comparing CD161− with CD161+ Treg cells in population III and found no significant differences between the percentages of Treg cells that express these markers on the two subpopulations, although there was a tendency to lower expression of CD39 (Fig. 4A). Likewise, we compared expression of FOXP3, RORC, CTLA-4 (essential for Treg-cell function ), ICOS (Inducible T-cell co-stimulator; ICOS+ Treg cells suppress DCs via IL-10 and TGF-β ), and Helios (a putative marker of thymically derived Treg cells ) by qRT-PCR on populations I CD161−, III CD161−, and III CD161+ Treg cells obtained from freshly sorted healthy donor Treg cells (Fig. 4B–G). As noted above, population III CD161+ Treg cells express less FOXP3 than the other populations (Fig. 4B) and variable basal levels of RORC with a tendency for higher expression in CD161+ cells (Fig. 4C), resulting in a quantitative FOXP3/RORC mRNA ratio in population III CD161+ Treg cells that favors RORC, compared with that of the other two populations (Fig. 4D).
Affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London, UK. email@example.com