title: TH17 cells express ST2 and are controlled by the alarmin IL-33 in the small intestine.
abstract: TH17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue inflammation is a beneficial host response to infection, but it can also contribute to autoimmunity. The crosstalk between a tissue and the immune system during an inflammatory response is key for preserving tissue integrity and restoring physiological processes. However, how the inflamed tissue regulates the magnitude of an immune response by controlling pro-inflammatory T cells is not well characterized so far. Here we show that TH17 cells accumulating in the small intestine upon inflammation express the IL-33 receptor (ST2) and intestinal epithelial cells (IEC) are the main source of the alarmin interleukin-33 (IL-33). We show that pro-inflammatory TH17 cells acquire a regulatory phenotype with immunosuppressive properties in response to IL-33. Absence of ST2 signaling promotes the secretion of pro-inflammatory cytokines by TH17 cells and dampens the secretion of IL-10. Our results provide new insights into the mechanisms by which IEC, via IL-33/ST2 axis, may control pro-inflammatory TH17 cells in the small intestine to sustain homeostasis.
authors.affiliation: Charité Universitätsmedizin-Berlin, Berlin, Germany.|Deutsches Rheuma Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Pascual-Reguant
authors.affiliation: Deutsches Rheuma Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Bayat Sarmadi
authors.affiliation: Deutsches Rheuma Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.|Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Baumann
authors.affiliation: Medizinische Mikrobiologie, Immunologie und Hygiene der TU München, München, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Noster
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, RNAi and Genome Integrity, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Cirera-Salinas
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: C
authors.initials: C
authors.lastname: Curato
authors.affiliation: I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Pelczar
authors.affiliation: I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Huber
authors.affiliation: Medizinische Mikrobiologie, Immunologie und Hygiene der TU München, München, Germany.|German Center for Infection Research (DZIF), Munich, Munich, Germany.
authors.forename: C E
authors.initials: CE
authors.lastname: Zielinski
authors.affiliation: Deutsches Rheuma Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.|Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Löhning
authors.affiliation: Charité Universitätsmedizin-Berlin, Berlin, Germany.|Deutsches Rheuma Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.
authors.forename: A E
authors.initials: AE
authors.lastname: Hauser
authors.affiliation: Charité Universitätsmedizin-Berlin, Berlin, Germany.|Deutsches Rheuma Forschungszentrum (DRFZ), a Leibniz Institute, Berlin, Germany.|Immunobiology Department, Yale School of Medicine, Connecticut, New Haven, USA.
authors.forename: E
authors.initials: E
authors.lastname: Esplugues
mesh_terms: D000067531:Alarmins / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006706:Homeostasis; D007249:Inflammation / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism*; D007421:Intestine, Small / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000067531:Alarmins; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D016753:Interleukin-10