title: CCR5 blockade combined with cyclosporine A attenuates liver GVHD by impairing T cells function.
abstract: OBJECTIVE
  Our preview study found that CCR5 blockade combined with cyclosporine A could attenuate the severity of liver GVHD. But the potential immunological mechanisms have not yet been explored. So our present study was designed to clarify the potential immunological mechanisms in mouse models after allo-HSCT.
  
  
  METHODS
  Firstly, we detected donor T cells homing to target organs, and analyzed the specific effector subsets in liver. Additionally, we assessed antigen-presenting cells (APCs), especially DCs and CD4+T cells differentiation in secondary lymphoid organs.
  
  
  RESULTS
  Data showed that MVC combined with CsA reduced donor T cells migration to target organs in vivo. MVC and CsA treatment reduced the amount of donor T cells in the absolute numbers, also in donor CD4+and CD8+T cells by targeting at CCR5. And MVC co-injected with CsA was capable of slightly suppressing DC maturation, and reduced the percentage of Th1 and Th17 mainly by noncompetitive combination of CCR5.
  
  
  CONCLUSIONS
  Combined use of MVC and CsA was effective in attenuating liver GVHD in murine model. It can suppress DC maturation, affect T cells differentiation, and reduce donor T cells homing to target organs. This may offer a novel therapeutic perspective approach for clinical liver GVHD after allo-HSCT.
authors.affiliation: Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China. renhy0813@163.com.
authors.forename: Hanyun
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Hematology, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
authors.forename: Shengchao
authors.initials: S
authors.lastname: Miao
mesh_terms: D000818:Animals; D065100:CCR5 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D000077592:Maraviroc; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019713:Receptors, CCR5 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D065100:CCR5 Receptor Antagonists; C000592874:CCR5 protein, mouse; D003510:Cyclohexanes; D016207:Cytokines; D007166:Immunosuppressive Agents; D019713:Receptors, CCR5; D014230:Triazoles; D016572:Cyclosporine; D000077592:Maraviroc
keywords: CCR5 blockade; Graft-versus-host disease; Murine model; T cells