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: To further characterize the population of interest, FOXP3 expression was evaluated. Population III CD161+ Treg cells expressed less FOXP3 protein in comparison with population III CD161− cells (Fig. 3A and B). Given the lower expression of FOXP3, and previous suggestions that population III is nonsuppressive , we tested their capacity to suppress proliferation of auto-logous CFSE-labeled Teff cells. We found that suppressive function in population III CD161+ Treg cells was similar to other Treg-cell populations (Fig. 3C and D). Likewise, their ability to suppress production of IFN-γ and IL-2 production from Teff cells was comparable to those of other Treg subpopulations (Fig. 3E and F). These data demonstrate that population III CD161+ cells have regulatory properties and further confirmed that these are not contaminating Teff cells of the Th17 or Th1 lineage.
Affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London, UK. firstname.lastname@example.org