Τίτλος:
IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2016 American Society for Investigative Pathology.
Συγγραφείς:
De Salvo, C.
Wang, X.-M.
Pastorelli, L.
Mattioli, B.
Omenetti, S.
Buela, K.A.
Chowdhry, S.
Garg, R.R.
Goodman, W.A.
Rodriguez-Palacios, A.
Smith, D.E.
Abbott, D.W.
Cominelli, F.
Bamias, G.
Xin, W.
Lee, J.J.
Vecchi, M.
Pizarro, T.T.
Περιοδικό:
American Journal of Pathology
Εκδότης:
HANLEY & BELFUS-ELSEVIER INC
Λέξεις-κλειδιά:
eotaxin; interleukin 33; cytokine; Il33 protein, mouse; interleukin 33, animal experiment; animal model; animal tissue; Article; cell infiltration; cellular immunity; chronic disease; colon mucosa; controlled study; disease course; eosinophil infiltration; eosinophilia; experimental disease; human; human tissue; ileitis; in vivo study; intestine mucosa; microbiome; mouse; nonhuman; priority journal; quantitative analysis; reverse transcription polymerase chain reaction; signal transduction; Th2 cell; upregulation; animal; cytology; disease model; eosinophil; ileitis; immunology; inflammation; metabolism; pathology; Th2 cell, Animals; Cytokines; Disease Models, Animal; Eosinophils; Ileitis; Inflammation; Interleukin-33; Intestinal Mucosa; Mice; Th2 Cells; Up-Regulation
DOI:
10.1016/j.ajpath.2015.11.028
