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

Abstract

Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4⁺ T_h2 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 ILC2₁₀. These cells produce IL-10 and downregulate some pro-inflammatory genes. Signals that generate ILC2₁₀ are distinct from those that induce IL-13 production, and gene expression data indicate that an alternative activation pathway leads to the generation of ILC2₁₀. In vivo, IL-2 enhances ILC2₁₀ generation and is associated with decreased eosinophil recruitment to the lung. Unlike most activated ILC2, the ILC2₁₀ 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.