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

Johanna Emgård, Hana Kammoun, Bethania García-Cassani, Julie Chesné, Sara M. Parigi, Jean Marie Jacob, Hung Wei Cheng, Elza Evren, Srustidhar Das, Paulo Czarnewski, Natalie Sleiers, Felipe Melo-Gonzalez, Egle Kvedaraite, Mattias Svensson, Elke Scandella, Matthew R. Hepworth, Samuel Huber, Burkhard Ludewig, Lucie Peduto, Eduardo J. VillablancaHenrique Veiga-Fernandes, João P. Pereira, Richard A. Flavell, Tim Willinger

Research output: Contribution to journalArticlepeer-review

131 Citations (Scopus)

Abstract

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 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,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. 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.

Original languageEnglish
Pages (from-to)120-132.e8
JournalImmunity
Volume48
Issue number1
DOIs
Publication statusPublished - 16 Jan 2018
Externally publishedYes

Keywords

  • cell migration
  • colon
  • EBI2
  • GPR183
  • inflammation
  • innate lymphoid cells
  • lymphoid tissue
  • oxysterols

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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