Differential Modulation of Human Innate Lymphoid Cell (ILC) Subsets by IL-10 and TGF-β

Using multiparameter flow cytometry human innate lymphoid cell (ILC) subsets can be detected in the circulation, in relatively low frequencies. Despite the low frequency of ILCs in circulation, ex vivo experiments have demonstrated that these ILCs release extremely large per cell quantities of signature ILC cytokines following activation. To determine how activated ILC cytokine production is regulated, ILC subsets were activated in the presence or absence of the immunoregulatory cytokines IL-10 and TGF-β. An examination of circulating ILC subsets revealed surface expression of IL-10Rα and mRNA expression of both IL-10Rα and TGF-βR1 for all ILC subsets. Stimulated ILC1 production of IFN-γ was decreased by TGF-β and not IL-10. Interestingly, ILC2s stimulated in the presence of IL-10 had a marked reduction in cytokine production of IL-5 and IL-13 while TGF-β had no effect on ILC2 cytokine production. Ex vivo activated ILC1 and ILC2 subsets were also found to be a source of the immunoregulatory cytokine IL-10, raising the potential for ILC-mediated regulation of immune cells. These findings demonstrate the differential effects of immunoregulatory cytokines IL-10 and TGF-β on activated ILC1 and ILC2 populations ex vivo.