Antibody Blockade of CCL25/CCR9 Ameliorates Early but not Late Chronic Murine Ileitis

Jesús Rivera-Nieves, Johnson Ho, Giorgos Bamias, Natalia Ivashkina, Klaus Ley, Martin Oppermann, Fabio Cominelli

Research output: Contribution to journalArticlepeer-review

121 Scopus citations


Background & Aims: CCL25 mediates the homeostatic recruitment of CCR9-expressing lymphocytes to the small intestine, but the function of this chemokine/receptor pair during chronic small intestinal inflammation has yet to be determined. Furthermore, although clinical trials to evaluate the efficacy of targeting the CCL25/CCR9 axis for the treatment of Crohn's disease are being conducted, preclinical data in animal models of IBD are lacking. Methods: In the current studies, we investigated the expression of CCL25 and CCR9 as a function of disease progression in a spontaneous murine model of chronic ileitis (SAMP1/YitFc) using flow cytometry, real-time reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. In addition, we assessed the functional role of the axis in the overall disease process through therapeutic studies that target the chemokine or the receptor during early and late disease. Results: The percentage of CCR9-expressing lymphocytes increased during early disease, accompanied by the appearance of a population of CCR9high lymphocytes, predominantly within CD8+ T cells. Yet different from patients with primary sclerosing cholangitis, the expression of CCL25 remained restricted to the small intestine, even in mice with inflammation of the biliary tree. Neutralization of the receptor or the chemokine attenuated early disease but showed no therapeutic efficacy during the later stages, when overall CCR9 expression decreased and the CCR9high population was absent. Conclusions: Our studies show that the role of this chemokine axis is not limited to homeostatic recruitment, as previously believed. However, these molecules appear to play their most crucial role during the early stages of chronic murine ileitis.

Original languageEnglish (US)
Pages (from-to)1518-1529
Number of pages12
Issue number5
StatePublished - Nov 2006
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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