title: Anti-CCL25 antibody prolongs skin allograft survival by blocking CCR9 expression and impairing splenic T-cell function.
abstract: Chemokines, by virtue of their ability to recruit immune cells into allografts, play critical roles in acute transplantation rejection. CCR9 and its ligand, CCL25, is one of the key regulators of thymocyte migration and maturation in normal and inflammatory conditions. Moreover, several studies have revealed that high expression of CCR9 and CCL25 participated in many kinds of diseases. However, the role of CCR9 in allograft rejection is still unclear. In this study, we established a murine skin transplantation model of acute rejection. Our findings showed that the proportion of CCR9-expressing T cells was significantly increased in the spleen of allotransplanted mice compared with syngeneic transplantation. Furthermore, expression of CCL25 in allograft was similarly increased. Neutralization of CCL25 by intravenous injection of anti-CCL25 monoclonal antibody significantly prolonged skin allograft survival, decreased the number of infiltrating cells, and simultaneously suppressed the chemotactic ability and the proliferation of the splenic T cells in response to allogeneic antigens. Finally, blockade of CCL25 also diminished the secretion of IFN-γ by splenic T cells. These studies indicated that CCR9/CCL25 was involved in acute transplantation rejection and anti-CCL25 strategies might be useful in preventing acute rejection.
authors: Department of Immunology, Wuhan University School of Medicine, Dong Hu Road 115, Wuchang, Wuhan 430071, People's Republic of China.
authors: Jie
authors: J
authors: Li
authors: Tao
authors: T
authors: Xiong
authors: Ruijing
authors: R
authors: Xiao
authors: Ali
authors: A
authors: Xiong
authors: Jie
authors: J
authors: Chen
authors: Ehtisham
authors: E
authors: Altaf
authors: Yingcheng
authors: Y
authors: Zheng
authors: Guoguo
authors: G
authors: Zhu
authors: Yuling
authors: Y
authors: He
authors: Jinquan
authors: J
authors: Tan
mesh_terms: D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D019742:Chemokines, CC / Q000037:antagonists & inhibitors* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054388:Receptors, CCR / Q000276:immunology*; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D016038:Skin Transplantation / Q000009:adverse effects / Q000276:immunology*; D013154:Spleen / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; C119309:CC chemokine receptor 9; C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D007166:Immunosuppressive Agents; D054388:Receptors, CCR; D007371:Interferon-gamma