TY - JOUR
TI - IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis
AU - De Salvo, C.
AU - Wang, X.-M.
AU - Pastorelli, L.
AU - Mattioli, B.
AU - Omenetti, S.
AU - Buela, K.A.
AU - Chowdhry, S.
AU - Garg, R.R.
AU - Goodman, W.A.
AU - Rodriguez-Palacios, A.
AU - Smith, D.E.
AU - Abbott, D.W.
AU - Cominelli, F.
AU - Bamias, G.
AU - Xin, W.
AU - Lee, J.J.
AU - Vecchi, M.
AU - Pizarro, T.T.
JO - American Journal of Pathology
PY - 2016
VL - 186
TODO - 4
SP - 885-898
PB - HANLEY & BELFUS-ELSEVIER INC
SN - 0002-9440
TODO - 10.1016/j.ajpath.2015.11.028
TODO - 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
TODO - 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.
ER -