BACKGROUND: CD4CD25 T cells induce severe colitis when injected into immunodeficient recipients. The migration of disease-inducing cells to the bowel is controlled by adhesion molecules and chemotactic proteins. Chemokine receptors expressed on the T cells are therefore potential targets for anti-inflammatory therapy in inflammatory bowel disease. In this study, we have investigated the role of the chemokine receptor CXCR3 in the development of chronic colitis in a murine model. METHOD: Expression of CXCR3 on CD4 T cell from normal and colitic mice was assessed by flow cytometry. Development of colitis was followed after transfer of either normal or CXCR3CD4CD25T cell into immunodeficient host. In addition, the ability of regulatory T cell to function in vivo in the absence of CXCR3 was tested. RESULTS: We find CXCR3 to be expressed on 80% to 90% of CD4 T cells isolated from colitic mice compared with only 4% to 10% of CD4 T cells in normal naïve mice. Injecting CD4CXCR3CD25 T cells into immunodeficient hosts results in an ameliorated form of colitis with a lack of clinical symptoms, suggesting that CXCR3 expression is important for enteroantigen priming of CD4 T cells and/or subsequent migration into the gut wall. In contrast, CXCR3 expression does not affect the function of regulatory T cells because CXCR3 regulatory T cells are just as capable as their wild-type counterpart of controlling disease development. The diminished disease-inducing capability of CXCR3 T cells is not caused by the absence of enteroantigen specificity; we also tested the enteroantigen-specific proliferative ability of CD4CD25 T cells from CXCR3 mice in vitro and found that they respond even more strongly than wild-type cells. CONCLUSIONS: The present data indicate that CXCR3 plays an important role in controlling the migration of disease-inducing CD4CD25 T cells into the gut wall. In contrast, lack of CXCR3 expression by regulatory T cells does not compromise their function in this model of colitis.
BACKGROUND:CD4CD25 T cells induce severe colitis when injected into immunodeficient recipients. The migration of disease-inducing cells to the bowel is controlled by adhesion molecules and chemotactic proteins. Chemokine receptors expressed on the T cells are therefore potential targets for anti-inflammatory therapy in inflammatory bowel disease. In this study, we have investigated the role of the chemokine receptor CXCR3 in the development of chronic colitis in a murine model. METHOD: Expression of CXCR3 on CD4 T cell from normal and colitic mice was assessed by flow cytometry. Development of colitis was followed after transfer of either normal or CXCR3CD4CD25T cell into immunodeficient host. In addition, the ability of regulatory T cell to function in vivo in the absence of CXCR3 was tested. RESULTS: We find CXCR3 to be expressed on 80% to 90% of CD4 T cells isolated from colitic mice compared with only 4% to 10% of CD4 T cells in normal naïve mice. Injecting CD4CXCR3CD25 T cells into immunodeficient hosts results in an ameliorated form of colitis with a lack of clinical symptoms, suggesting that CXCR3 expression is important for enteroantigen priming of CD4 T cells and/or subsequent migration into the gut wall. In contrast, CXCR3 expression does not affect the function of regulatory T cells because CXCR3 regulatory T cells are just as capable as their wild-type counterpart of controlling disease development. The diminished disease-inducing capability of CXCR3 T cells is not caused by the absence of enteroantigen specificity; we also tested the enteroantigen-specific proliferative ability of CD4CD25 T cells from CXCR3mice in vitro and found that they respond even more strongly than wild-type cells. CONCLUSIONS: The present data indicate that CXCR3 plays an important role in controlling the migration of disease-inducing CD4CD25 T cells into the gut wall. In contrast, lack of CXCR3 expression by regulatory T cells does not compromise their function in this model of colitis.
Authors: Jerod A Skyberg; Amy Robison; Sarah Golden; Maryclare F Rollins; Gayle Callis; Eduardo Huarte; Irina Kochetkova; Mark A Jutila; David W Pascual Journal: J Leukoc Biol Date: 2011-06-21 Impact factor: 4.962
Authors: Venkata S Kotakadi; Yu Jin; Anne B Hofseth; Lei Ying; Xiangli Cui; Suresh Volate; Alexander Chumanevich; Patricia A Wood; Robert L Price; Anna McNeal; Udai P Singh; Narendra P Singh; Mitzi Nagarkatti; Prakash S Nagarkatti; Lydia E Matesic; Karine Auclair; Michael J Wargovich; Lorne J Hofseth Journal: Carcinogenesis Date: 2008-06-20 Impact factor: 4.944
Authors: Ravindra Uppaluri; Kathleen C F Sheehan; Liqing Wang; Jack D Bui; Joshua J Brotman; Bao Lu; Craig Gerard; Wayne W Hancock; Robert D Schreiber Journal: Transplantation Date: 2008-07-15 Impact factor: 4.939
Authors: Francoise Bachelerie; Adit Ben-Baruch; Amanda M Burkhardt; Christophe Combadiere; Joshua M Farber; Gerard J Graham; Richard Horuk; Alexander Hovard Sparre-Ulrich; Massimo Locati; Andrew D Luster; Alberto Mantovani; Kouji Matsushima; Philip M Murphy; Robert Nibbs; Hisayuki Nomiyama; Christine A Power; Amanda E I Proudfoot; Mette M Rosenkilde; Antal Rot; Silvano Sozzani; Marcus Thelen; Osamu Yoshie; Albert Zlotnik Journal: Pharmacol Rev Date: 2013-11-11 Impact factor: 25.468