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. email@example.comShow MeSH
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Mentions: Given the relatively small changes in transcription factor profiles observed (Fig. 1E) and the relatively low frequency of conversion seen with ICS (Fig. 1B) in “whole” bead-enriched CD4+CD25+ Treg cells, we hypothesized that IL-17 potential is restricted to one or more subpopulations of human Treg cells. Treg cells were FACS sorted into three subpopulations based on the expression of FOXP3 and CD45RA, namely CD4+CD25++CD127loCD45RA+ (population I), CD4+CD25+++CD127loCD45RA− (population II), and CD4+CD25++CD127loCD45RA− (population III), as recently published  (Fig. 2A and Supporting Information Fig. 4). Following stimulation in vitro in the presence of IL-1β and IL-1β+IL-2, only population III was found to produce IL-17 (Fig. 2B).
Affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London, UK. firstname.lastname@example.org