Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4705K) PDF+supp data (5729K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Taylor, B. C. Articles by Artis, D. Search for Related Content PubMed PubMed Citation Articles by Taylor, B. C. Articles by Artis, D. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Related Collections Related Article Social Bookmarking                            What's this?

¹ Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104
² Inflammation Research, Amgen Inc., Seattle, WA 98119

CORRESPONDENCE David Artis: dartis{at}vet.upenn.edu

Intestinal epithelial cells (IECs) 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) , and IL-17A, and development of severe intestinal inflammation. Critically, neutralization of IFN- in Trichuris-infected TSLPR^–/– mice 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-, and developed heightened intestinal inflammation upon exposure to dextran sodium sulfate, demonstrating a previously unrecognized immunoregulatory role for TSLP in a mouse model of inflammatory bowel disease.

© 2009 Taylor et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

TSLP calms inflammation

Amy Maxmen
J. Exp. Med. 2009 206: 493. [Full Text] [PDF]

This article has been cited by other articles:

• Maizels, R. M., Pearce, E. J., Artis, D., Yazdanbakhsh, M., Wynn, T. A. (2009). Regulation of pathogenesis and immunity in helminth infections. JEM 206: 2059-2066 [Abstract] [Full Text]  
• Massacand, J. C., Stettler, R. C., Meier, R., Humphreys, N. E., Grencis, R. K., Marsland, B. J., Harris, N. L. (2009). Helminth products bypass the need for TSLP in Th2 immune responses by directly modulating dendritic cell function. Proc. Natl. Acad. Sci. USA 106: 13968-13973 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS