Editors' ChoiceInflammation

ILCregs: The new kid in class

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Science Translational Medicine  06 Sep 2017:
Vol. 9, Issue 406, eaao6121
DOI: 10.1126/scitranslmed.aao6121


ILCregs are a population of innate lymphoid cells that control innate intestinal inflammation through IL-10.

School is back in session, and there’s a new name on the innate lymphoid cell (ILC) class roster. ILCs, which already include natural killer cells, lymphoid tissue inducer cells, ILC1s, ILC2s, and ILC3s, are an important subset of innate tissue-resident immune cells involved in tissue homeostasis and inflammation. Now, Wang et al. introduce ILCregs, a new regulatory subset of ILCs.

The authors discovered ILCregs in murine and human intestines, where they produce the regulatory cytokine interleukin-10 (IL-10). Although they share key surface markers with other ILC subsets and regulatory T cells (Tregs), ILCregs are defined by a distinct transcriptional profile that differs from that of other ILC subsets and includes preferential expression of transcription factors Id3 and Sox4 but not other ILC or Treg lineage–defining factors. Moreover, the authors demonstrate that ILCregs depend on Id3 for their development and derive from a subset of common helper-like innate lymphoid precursors separate from that of other ILCs.

So what’s this new kid all about? Intestinal ILCreg numbers and their production of IL-10 and transforming growth factor–β (TGF-β) expanded dramatically after various inflammatory insults. Notably, autocrine production of TGF-β was required for this inflammation-dependent expansion of ILCregs but not for their development. Using mice lacking adaptive immune cells, the authors found that ILCregs limited innate intestinal inflammation in an IL-10 dependent manner. ILCregs specifically reduced inflammatory cytokine production by intestinal ILC1s and ILC3s but not ILC2s. Intriguingly, the authors found that Tregs alone were insufficient to regulate innate-type inflammation in their model, suggesting a distinct role for ILCregs.

Collectively these findings hint at a paradigm wherein ILCregs preferentially control intestinal inflammation mediated by innate cell types. We will next want to know whether ILCregs reside in other tissues with well-defined ILC populations—such as skin, lung, and fat—and whether their functions there are similar. Armed with tools for ILCreg lineage-specific depletion, it will also be of interest to explore the homeostatic role of ILCregs under noninflammatory conditions and to define the contexts in which ILCregs and Tregs provide discrete versus overlapping contributions to immune regulation. Thus, keep an eye on the ILCreg—the kid shows potential.

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