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

  • Emgård J Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
  • Kammoun H Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
  • García-Cassani B Champalimaud Research, Champalimaud Centre for the Unknown, 1400-038 Lisboa, Portugal.
  • Chesné J Champalimaud Research, Champalimaud Centre for the Unknown, 1400-038 Lisboa, Portugal.
  • Parigi SM Immunology & Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
  • Jacob JM Unité Stroma, Inflammation & Tissue Repair, Institut Pasteur, 75724 Paris, France; INSERM U1224, 75724 Paris, France.
  • Cheng HW Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.
  • Evren E Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
  • Das S Immunology & Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
  • Czarnewski P Immunology & Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
  • Sleiers N Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
  • Melo-Gonzalez F Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9PL, UK.
  • Kvedaraite E Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
  • Svensson M Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden.
  • Scandella E Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.
  • Hepworth MR Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9PL, UK.
  • Huber S I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Ludewig B Institute of Immunobiology, Kantonsspital St. Gallen, 9007 St. Gallen, Switzerland.
  • Peduto L Unité Stroma, Inflammation & Tissue Repair, Institut Pasteur, 75724 Paris, France; INSERM U1224, 75724 Paris, France.
  • Villablanca EJ Immunology & Allergy Unit, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
  • Veiga-Fernandes H Champalimaud Research, Champalimaud Centre for the Unknown, 1400-038 Lisboa, Portugal.
  • Pereira JP Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Flavell RA Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute. Electronic address: richard.flavell@yale.edu.
  • Willinger T Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: tim.willinger@ki.se.
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  • 2018-01-19
Published in:
  • Immunity. - 2018
EBI2
GPR183
cell migration
colon
inflammation
innate lymphoid cells
lymphoid tissue
oxysterols
Animals
Cell Movement
Colitis
Colon
Cytokines
Flow Cytometry
Fluorescent Antibody Technique
Ligands
Lymphocytes
Lymphoid Tissue
Mice
Oxysterols
Real-Time Polymerase Chain Reaction
Receptors, G-Protein-Coupled
Signal Transduction
English 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.
Language
  • English
Open access status
hybrid
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Persistent URL
https://folia.unifr.ch/global/documents/77205
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