GSE117470
Tissue signals imprint ILC2 identity with anticipatory function [RNA-Seq]
Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP).  Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s according to their tissue of origin, even in the setting of combined IL-25, IL-33R and TSLPR-deficiency.  Single-cell profiling confirmed a tissue-organizing transcriptome and identified ILC2 subsets expressing distinct activating receptors, including the major subset of skin ILC2s, which were activated preferentially by IL-18.  Tissue ILC2 subsets were normal in germ- free mice, suggesting that endogenous, tissue-derived, signals drive the maturation of ILC2 subsets by controlling expression of distinct patterns of activating receptors, thus anticipating tissue-specific patterns to perturbations occurring later in life. Overall design: 8-14 week old male WT or TKO (triple-deficient Crlf2-/-Il25-/-Il1rl1-/-) ILC2 reporter mice were used to sort steady-state activated ILC2s from bone marrow (WT n=3; TKO n=3), fat (visceral adipose tissue; WT n=6, TKO n=4); lung (WT n=5, TKO n=5), small intestine lamina propia (WT n=6; TKO n=5) and skin ( WT n=6, TKO n=5). One of the lung TKO samples and 2 of the small intestine TKO samples failed library prep. All other samples were included in the analyses.