@article{3101216,
    title = "IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis",
    author = "De Salvo, C. and Wang, X.-M. and Pastorelli, L. and Mattioli, B. and Omenetti, S. and Buela, K.A. and Chowdhry, S. and Garg, R.R. and Goodman, W.A. and Rodriguez-Palacios, A. and Smith, D.E. and Abbott, D.W. and Cominelli, F. and Bamias, G. and Xin, W. and Lee, J.J. and Vecchi, M. and Pizarro, T.T.",
    journal = "American Journal of Pathology",
    year = "2016",
    volume = "186",
    number = "4",
    pages = "885-898",
    publisher = "HANLEY & BELFUS-ELSEVIER INC",
    issn = "0002-9440",
    doi = "10.1016/j.ajpath.2015.11.028",
    keywords = "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",
    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 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."
}