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

First Author  Taylor BC Year  2009
Journal  J Exp Med Volume  206
Issue  3 Pages  655-67
PubMed ID  19273626 Mgi Jnum  J:146749
Mgi Id  MGI:3838407 Doi  10.1084/jem.20081499
Citation  Taylor BC, et al. (2009) TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J Exp Med 206(3):655-67
abstractText  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) gamma, and IL-17A, and development of severe intestinal inflammation. Critically, neutralization of IFN-gamma 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-gamma, 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.
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