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

IL-33 Interleukin-33 Drives Eosinophil Infiltration and Pathogenic Type 2 Helper T-Cell Immune Responses Leading to Chronic Experimental Ileitis. Am J Pathol. 2016 Feb 20; Authors: De Salvo C, Wang XM, Pastorelli L, Mattioli B, Omenetti S, Buela KA, Chowdhry S, Garg RR, Goodman WA, Rodriguez-Palacios A, Smith DE, Abbott DW, Cominelli F, Bamias G, Xin W, Lee JJ, Vecchi M, Pizarro TT Abstract 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 on 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 eosinophil in the colonic mucosa of inflammatory bowel disease patients versus noninflamed controls. Finally, colonization of commensal flor...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research