Characterization of an alternatively activated IL-10 producing innate lymphoid type-2 effector cell population

Abstract

Abstract Type-2 innate lymphoid (ILC2) cells share cytokine and transcription factor expression with CD4+ Th2 cells, but it is unknown if this ILC subtype undergoes functional diversification. Here, we report in vivo induction of a molecularly distinct subset of activated lung ILC2 cells, termed ILC210 cells, that produce IL-10 and downregulate genes associated with inflammation. Signals that generate ILC210 cells were distinct from those that induced IL-13 production and, along with transcriptome data, suggested an alternative pathway of activation. In vivo, IL-2 greatly enhanced ILC210 cell generation by IL-33 and was associated with decreased eosinophil recruitment to the lung. Unlike the majority of activated ILC2 cells, the ILC210 cell population underwent contraction following cessation of IL-33 stimulation in vivo, but with maintenance of a subpopulation of cells that can be recalled by restimulation, analogous to T cell effector cell and memory cell generation. Together, these data demonstrate previously unappreciated heterogeneity in the ILC2 cell response.