IL-33 Drives Eosinophil Infiltration and Pathogenic Type 2 Helper T-Cell Immune Responses Leading to Chronic Experimental Ileitis.

Autor:	De Salvo C; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese and Department of Biomedical Sciences, University of Milan, Milan, Italy., Wang XM; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Pastorelli L; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese and Department of Biomedical Sciences, University of Milan, Milan, Italy., Mattioli B; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Omenetti S; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Buela KA; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Chowdhry S; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio., Garg RR; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Goodman WA; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Rodriguez-Palacios A; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio., Smith DE; Inflammation Research, Amgen, Seattle, Washington., Abbott DW; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Cominelli F; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio., Bamias G; Academic Department of Gastroenterology, Kapodistrian University of Athens and Laikon Hospital, Athens, Greece., Xin W; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio., Lee JJ; Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Scottsdale, Arizona., Vecchi M; Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese and Department of Biomedical Sciences, University of Milan, Milan, Italy., Pizarro TT; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address: theresa.pizarro@case.edu.
Jazyk:	angličtina
Zdroj:	The American journal of pathology [Am J Pathol] 2016 Apr; Vol. 186 (4), pp. 885-98. Date of Electronic Publication: 2016 Feb 22.
DOI:	10.1016/j.ajpath.2015.11.028
Abstrakt:	Although a clear association has been established between IL-33 and inflammatory bowel disease, mechanistic studies to date, primarily using acute murine models of colitis, have yielded contradicting results, demonstrating both pathogenic and protective roles. We used a well-characterized, spontaneous model of inflammatory bowel disease [ie, SAMP1/YitFc (SAMP) mice] to investigate the role of IL-33 during chronic intestinal inflammation. Our results showed marked eosinophil infiltration into the gut mucosa with increased levels of eotaxins and type 2 helper T-cell (Th2) cytokines as disease progressed and became more severe, which could be reversed upon either eosinophil depletion or blockade of IL-33 signaling. Exogenous IL-33 administration recapitulated these effects in ilea of uninflamed (parental) control AKR/J mice. Human data supported these findings, showing colocalization and up-regulation of IL-33 and eosinophils in the colonic mucosa of inflammatory bowel disease patients versus noninflamed controls. Finally, colonization of commensal flora by fecal material transplantation into germ-free SAMP and the presence of the gut microbiome induced IL-33, subsequent eosinophil infiltration, and mounting of Th2 immune responses, leading to exacerbation of chronic intestinal inflammation characteristic of SAMP mice. These data demonstrate a pathogenic role for IL-33-mediated eosinophilia and activation of Th2 immunity in chronic intestinal inflammation that is dependent on the gut microbiome. Targeting IL-33 may represent a novel therapeutic approach to treat patients with inflammatory bowel disease. (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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