TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis

Betsy C. Taylor, Colby Zaph, Amy E. Troy, Yurong Du, Katherine J. Guild, Michael R. Comeau, David Artis

Research output: Contribution to journalArticleResearchpeer-review

293 Citations (Scopus)

Abstract

Intestinal epithelial cells(lECs) produce thymic stromal lymphopoietin(TSLP); however, the in vivo influence of TSLP-TSLP receptor(TSLPR) interactions on immunity and inflammation in the intestine remains unclear. We show that TSLP-TSLPR interactions are critical for immunity to the intestinal pathogen Trichuris. Monoclonal antibody-mediated neutralization of TSLP or deletion of the TSLPR in normally resistant mice resulted in defective expression of Th2 cytokines and persistent infection. Susceptibility was accompanied by elevated expression of interleukin(IL) 12/23p40, interferon(IFN) γIL-17A, and development of severe intestinal inflammation. Critically, neutralization of IFN-γ in Trichu- ris-infected TSLPR -/- restored Th2 cytokine responses and resulted in worm expulsion, providing the first demonstration of TSLPR-independent pathways for Th2 cytokine production. Additionally, TSLPR -/- mice displayed elevated production of IL-12/23p40 and IFN-γ, and developed heightened intestinal inflammation upon exposure to dextran sodium sul- fate, demonstrating a previously unrecognized immunoregulatory role for TSLP in a mouse model of inflammatory bowel disease.

Original languageEnglish
Pages (from-to)655-667
Number of pages13
JournalJournal of Experimental Medicine
Volume206
Issue number3
DOIs
Publication statusPublished - 16 Mar 2009
Externally publishedYes

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