Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation

Summary Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid‐tissue‐inducer (LTi) phenotype expressed G‐protein‐coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7&agr;,25‐hydroxycholesterol (7&agr;,25‐OHC). In mice lacking Gpr183 or 7&agr;,25‐OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation‐induced increased oxysterol production caused colitis through GPR183‐mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol‐GPR183‐dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Graphical Abstract Figure. No Caption available. HighlightsILC3s sense cholesterol metabolites (oxysterols) through the receptor GPR183GPR183 and its ligand 7&agr;,25‐OHC promote ILC3 migration to CPs and ILFsGPR183 and 7&agr;,25‐OHC are critical for CP and ILF formation in the colonGPR183 controls inflammatory tissue remodeling during immune‐mediated colitis &NA; ILC3s maintain healthy organ function in the intestine, but how ILC3s directly detect environmental cues is poorly understood. Emgård et al. find that GPR183 and oxysterols control the localization and LTi function of ILC3s and thereby promote the formation of colonic lymphoid tissues in the steady state and inflammation.

• Publication year

  2018

• Venue

  Immunity

• Publication date

  2018-01-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.immuni.2017.11.020PMID 29343433PMCID 5772175
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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