Innate lymphoid cells (ILCs) regulate homeostasis and protective immunity in the intestine. In Cell, Fan and colleagues identify a population of intestinal regulatory ILCs that expands after pathogenic stimulation and inhibits innate immune responses. Lin−CD45+CD127+IL-10+ cells in the lamina propria and epithelium of the small intestine of mice and humans have an expression and transcriptional profile characteristic of ILCs (Il10, Il7r, Il2ra, Id2 and Ly6a) do not express genes encoding markers specific for the ILC1, ILC2 and ILC3 subsets (Rorc, Tbx21, Gata3) or regulatory T cells (Foxp3 and Cd4) and specifically express the transcription factor Id3 and the cytokine receptors TGF-βR and IL-2R. They develop from α4β7+Id2hi progenitor cells that generate all lymphoid-tissue–inducer cells and ILCs and are the only ILC subset affected by deletion of Id3. Regulatory ILCs reach peak population expansion in Rag1−/− mice on day 8 after treatment with inflammatory stimuli and produce TGF-β1 (which is required for their proliferation and survival in an autocrine manner) and IL-10 (which suppresses the activation of ILC1 and ILC3 cells). Regulatory T cells have no substantial inhibitory effect on ILC activation, which indicates that regulatory ILCs are essential in resolving innate intestinal inflammation.

Cell (24 August 2017) doi:10.1016/j.cell.2017.07.027