title: Epithelial IL-1R2 acts as a homeostatic regulator during remission of ulcerative colitis.
abstract: Ulcerative colitis (UC) is a chronic intestinal inflammatory disease that may undergo periods of activity followed by remission. We aimed to identify the endogenous regulatory mechanisms that may promote disease remission. Transcriptional and protein analysis of the intestinal mucosa revealed that the IL-1 decoy receptor, interleukin-1 receptor type 2 (IL1R2), was upregulated in remission compared with active UC and controls. We identified epithelial cells as being responsible for increased IL-1R2 production during remission. Expression of IL1R2 was negatively regulated by Wnt/beta-catenin signals in colonic crypts or epithelial stem cell cultures; accordingly, epithelial stem cells upregulated IL-1R2 upon differentiation. Blocking IL-1R2 in isolated colonic crypt cultures of UC patients in remission and T-cell cultures stimulated with biopsy supernatant from UC patients in remission boosted IL-1β-dependent production of inflammation-related cytokines. Finally, IL1R2 transcription was significantly lower in patients that relapsed during a 1-year follow-up period compared with those in endoscopic remission. Collectively, our results reveal that the IL-1/IL-1R2 axis is differentially regulated in the remitting intestinal mucosa of UC patients. We hypothesize that IL-1R2 in the presence of low concentrations of IL-1β may act locally as a regulator of intestinal homeostasis.
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Mora-Buch
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Dotti
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.|Bioinformatics Platform, CIBERehd, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Planell
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Calderón-Gómez
authors.affiliation: Oncology Program, Institute for Research in Biomedicine Barcelona (IRB Barcelona), Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Jung
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Masamunt
authors.affiliation: Endoscopy Unit, Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Llach
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ricart
authors.affiliation: Oncology Program, Institute for Research in Biomedicine Barcelona (IRB Barcelona), Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Batlle
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Panés
authors.affiliation: Department of Gastroenterology, IDIBAPS, Hospital Clínic, CIBERehd, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Salas
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006706:Homeostasis; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics / Q000378:metabolism*; D012075:Remission, Spontaneous; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: C508592:IL1R2 protein, human; D053583:Interleukin-1beta; D053574:Receptors, Interleukin-1 Type II; D051153:Wnt Proteins; D051176:beta Catenin