Alternative activation generates IL-10 producing type 2 innate lymphoid cells.

Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4 T2 cells, but functional diversity of the ILC2 lineage has yet to be fully explored. Here, we show induction of a molecularly distinct subset of activated lung ILC2, termed ILC2. These cells produce IL-10 and downregulate some pro-inflammatory genes. Signals that generate ILC2 are distinct from those that induce IL-13 production, and gene expression data indicate that an alternative activation pathway leads to the generation of ILC2. In vivo, IL-2 enhances ILC2 generation and is associated with decreased eosinophil recruitment to the lung. Unlike most activated ILC2, the ILC2 population contracts after cessation of stimulation in vivo, with maintenance of a subset that can be recalled by restimulation, analogous to T-cell effector cell and memory cell generation. These data demonstrate the generation of a previously unappreciated IL-10 producing ILC2 effector cell population.