| Autor: |
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. |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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