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Tissue signals imprint ILC2 identity with anticipatory function.

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

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.

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