Abstract
Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4+ Th2 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.
Highlights
Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4+ Th2 cells, but functional diversity of the ILC2 lineage has yet to be fully explored
To identify gene expression changes associated with IL-33-induced ILC2 activation, we performed RNA-seq on sorted lung ILC2 from mice injected with either vehicle or IL-33
IL-33-mediated ILC2 activation led to other significant changes in gene expression (Fig. 1d), including upregulation of Klrg[1] and Mki[67], encoding cell activation and proliferation markers (Fig. 1e), and Il13, Il6, and Arg[1] (Fig. 1g), involved in proliferation and inflammatory functions of ILC211
Summary
Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4+ Th2 cells, but functional diversity of the ILC2 lineage has yet to be fully explored. 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. Cells of the innate immune system termed innate lymphoid cells (ILC), have been identified in mice and humans, and helper-like ILC have many parallels to CD4+ helper T (Th) effector cell subsets[1], despite a lack of antigen receptors In this regard, some subsets within the type 1 ILC (ILC1), ILC2, and type 3 (ILC3) populations have been compared to Th1, Th2, and Th17 cells, respectively. The ILC210 population undergoes contraction upon removal of stimulus, and can be recalled with subsequent challenge These cells decrease expression of some genes associated with inflammation, and when induced in vivo, are associated with a decrease in eosinophil recruitment to the lung. ILC210 can be induced by chronic exposure to the allergen papain, with the extent of induction correlating with the degree of activation of ILC2 and the inflammatory response
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