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Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0000000000000059
Original Basic Science Articles

CCL25/CCR9 Interactions Are Not Essential for Colitis Development but Are Required for Innate Immune Cell Protection from Chronic Experimental Murine Colitis

Wurbel, Marc-André PhD*,‡; Le Bras, Severine PhD†,‡; Ibourk, Mouna*,‡; Pardo, Michael*,‡; McIntire, Maria G. MD§; Coco, Dominique MD§; Geha, Raif S. MD†,‡; Fiebiger, Edda PhD*,‡; Snapper, Scott B. MD, PhD*,‡

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Abstract

Background:

The chemokine CCL25, and its receptor CCR9, constitute a unique chemokine/receptor pair, which regulates trafficking of T lymphocytes to the small intestine under physiological conditions and is an attractive target for small bowel Crohn's disease drug development. We have previously shown that CCL25/CCR9 interactions regulate the recovery from acute dextran sulfate sodium–induced colonic inflammation. In this study, we explored whether these interactions also regulate chronic colitis development in 2 independent murine models of experimental colitis.

Methods:

Histological flow cytometry and qPCR analyses were performed to evaluate the role of CL25 and CCR9 in chronic colonic inflammation induced by serial exposures to dextran sulfate sodium salts or by adoptive transfer of CD45RBhi CD4+ T cell into lymphopenic mice devoid of CCL25/CCR9 interactions.

Results:

Chronic dextran sulfate sodium exposure results in exacerbated colitis in mice deficient for either CCR9 or CCL25 when compared with wild-type control mice. Although CCR9-deficient T cells traffic to the colon and induce severe colitis similar to wild-type T cells in the CD45RB transfer model, naive wild-type T cells induce more severe disease in recipient animals devoid of CCL25 expression.

Conclusions:

CCL25/CCR9 interactions are required for modulating protection against large intestinal inflammation in 2 models of chronic colitis. These data may have implications for the potential effects of disrupting CCL25/CCR9 interactions in humans in the setting of intestinal disorders including inflammatory bowel disease.

Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.

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