Tissue signals imprint ILC2 identity with anticipatory function

Roberto R. Ricardo-Gonzalez, Steven J. Van Dyken, Christoph Schneider, Jinwoo Lee, Jesse C. Nussbaum, Hong Erh Liang, Dedeepya Vaka, Walter L. Eckalbar, Ari B. Molofsky, David J. Erle, Richard M. Locksley

Research output: Contribution to journalArticlepeer-review

265 Scopus citations


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-33-receptor-, and TSLP-receptor-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 unaltered in number and expression 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 perturbations occurring later in life.

Original languageEnglish
Pages (from-to)1093-1099
Number of pages7
JournalNature immunology
Issue number10
StatePublished - Oct 1 2018


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