title: CCL25/CCR9 interactions are not essential for colitis development but are required for innate immune cell protection from chronic experimental murine colitis.
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 CD45RB(hi) 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.
authors.affiliation: Divisions of *Gastroenterology/Nutrition and †Immunology, Boston Children's Hospital; ‡Department of Pediatrics, Harvard Medical School; and §Department of Pathology, Brigham and Women's Hospital & Harvard Medical School, Boston, Massachusetts.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Wurbel
authors.forename: Severine
authors.initials: S
authors.lastname: Le Bras
authors.forename: Mouna
authors.initials: M
authors.lastname: Ibourk
authors.forename: Michael
authors.initials: M
authors.lastname: Pardo
authors.forename: Maria G
authors.initials: MG
authors.lastname: McIntire
authors.forename: Dominique
authors.initials: D
authors.lastname: Coco
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
authors.forename: Edda
authors.initials: E
authors.lastname: Fiebiger
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
mesh_terms: D000818:Animals; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism*; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000503:physiopathology*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D011897:Random Allocation; D054388:Receptors, CCR / Q000276:immunology / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D054388:Receptors, CCR