Modulation of human innate lymphoid cell function by IL-10

Abstract

Abstract Although present in extremely low numbers in the human circulation at steady state, innate lymphoid cells (ILCs) are expanded in human helminth infections. Despite their low frequency (accounting for 0.21% (range 0.023–3.58%) of lymphocytes in the peripheral blood under homeostatic conditions), ILCs release extremely large quantities of cytokines following activation. If left unchecked, these cytokines can have deleterious effects on the host. We have observed that circulating ILCs demonstrate surface expression of IL-10R under homeostatic conditions. To examine how the expression of IL-10R regulates cytokine production by ILCs, ILC subsets were isolated from the peripheral blood of healthy donors by flow cytometry-based sorting and activated in the presence or absence of the immunoregulatory cytokine IL-10. ILCs stimulated in the presence of IL-10 had a marked reduction (range from 2–3.6 fold) in cytokines (IL-4, IL-5, IL-13, IL-17A, INF-γ, and TNF-α) when compared to ILCs activated without IL-10. These findings demonstrate that IL-10 signaling can inhibit cytokine production by activated ILCs. Furthermore, studies are currently underway to examine ILC subsets in the context of chronic helminth infections, where IL-10 has a modulatory effect on innate and adaptive immune cells and to identify additional mechanisms that regulate ILC cytokine production, including TGF-β.