IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis

Carlo De Salvo, Xiao Ming Wang, Luca Pastorelli, Benedetta Mattioli, Sara Omenetti, Kristine A. Buela, Saleem Chowdhry, Rekha R. Garg, Wendy A. Goodman, Alex Rodriguez-Palacios, Dirk E. Smith, Derek W. Abbott, Fabio Cominelli, Giorgos Bamias, Wei Xin, James J. Lee, Maurizio Vecchi, Theresa T. Pizarro

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)885-898
Number of pages14
JournalAmerican Journal of Pathology
Volume186
Issue number4
DOIs
StatePublished - Apr 1 2016

Fingerprint

Ileitis
Th2 Cells
Eosinophils
Inflammatory Bowel Diseases
Inflammation
Mucous Membrane
Inbred AKR Mouse
Interleukin-33
Eosinophilia
Colitis
Ileum
Immunity
Up-Regulation
Cytokines

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis. / De Salvo, Carlo; Wang, Xiao Ming; Pastorelli, Luca; Mattioli, Benedetta; Omenetti, Sara; Buela, Kristine A.; Chowdhry, Saleem; Garg, Rekha R.; Goodman, Wendy A.; Rodriguez-Palacios, Alex; Smith, Dirk E.; Abbott, Derek W.; Cominelli, Fabio; Bamias, Giorgos; Xin, Wei; Lee, James J.; Vecchi, Maurizio; Pizarro, Theresa T.

In: American Journal of Pathology, Vol. 186, No. 4, 01.04.2016, p. 885-898.

Research output: Contribution to journalArticle

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 2016, 'IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis', American Journal of Pathology, vol. 186, no. 4, pp. 885-898. https://doi.org/10.1016/j.ajpath.2015.11.028
De Salvo, Carlo ; Wang, Xiao Ming ; Pastorelli, Luca ; Mattioli, Benedetta ; Omenetti, Sara ; Buela, Kristine A. ; Chowdhry, Saleem ; Garg, Rekha R. ; Goodman, Wendy A. ; Rodriguez-Palacios, Alex ; Smith, Dirk E. ; Abbott, Derek W. ; Cominelli, Fabio ; Bamias, Giorgos ; Xin, Wei ; Lee, James J. ; Vecchi, Maurizio ; Pizarro, Theresa T. / IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis. In: American Journal of Pathology. 2016 ; Vol. 186, No. 4. pp. 885-898.
@article{6b15ed63c5154d089a086bf37417b087,
title = "IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis",
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.",
author = "{De Salvo}, Carlo and Wang, {Xiao Ming} and Luca Pastorelli and Benedetta Mattioli and Sara Omenetti and Buela, {Kristine A.} and Saleem Chowdhry and Garg, {Rekha R.} and Goodman, {Wendy A.} and Alex Rodriguez-Palacios and Smith, {Dirk E.} and Abbott, {Derek W.} and Fabio Cominelli and Giorgos Bamias and Wei Xin and Lee, {James J.} and Maurizio Vecchi and Pizarro, {Theresa T.}",
year = "2016",
month = "4",
day = "1",
doi = "10.1016/j.ajpath.2015.11.028",
language = "English (US)",
volume = "186",
pages = "885--898",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - IL-33 drives eosinophil infiltration and pathogenic type 2 helper T-cell immune responses leading to chronic experimental ileitis

AU - De Salvo, Carlo

AU - Wang, Xiao Ming

AU - Pastorelli, Luca

AU - Mattioli, Benedetta

AU - Omenetti, Sara

AU - Buela, Kristine A.

AU - Chowdhry, Saleem

AU - Garg, Rekha R.

AU - Goodman, Wendy A.

AU - Rodriguez-Palacios, Alex

AU - Smith, Dirk E.

AU - Abbott, Derek W.

AU - Cominelli, Fabio

AU - Bamias, Giorgos

AU - Xin, Wei

AU - Lee, James J.

AU - Vecchi, Maurizio

AU - Pizarro, Theresa T.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84962508048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962508048&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2015.11.028

DO - 10.1016/j.ajpath.2015.11.028

M3 - Article

C2 - 26908008

AN - SCOPUS:84962508048

VL - 186

SP - 885

EP - 898

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 4

ER -