title: Different Effects of Tacrolimus on Innate and Adaptive Immune Cells in the Allograft Transplantation.
abstract: While tacrolimus (FK506) is currently used as immunosuppression therapy in transplant recipient, the immunological mechanism remains unknown. Herein, the immunoregulatory effects of FK506 were investigated in the physiological status and allogeneic skin transplantation. FK506 cannot significantly alter the functions of innate immune cells (macrophages and neutrophils) and adaptive immune cells (T cells) in the physiological status. However, it can effectively delay allogeneic skin-graft rejection through ameliorating the T cell responses, but not myeloid-derived innate immune cell responses. Importantly, it did not affect the allograft recipient macrophage innate immune defence capacity to bacteria. In clinics, FK506 treatment can significantly control the cytokine production in T cells, but not non-T cells. This study shows targeting calcineurin signalling, FK506, to be essential in inducing allograft tolerance, but not to damage the innate defence capacity, validating the immune cell phenotypes as a potential marker in transplantation following FK506 treatment.
authors.affiliation: Ruijin Hospital and Medical School of Shanghai Jiao Tong University, Shanghai, China.|Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Biotherapy Research Center, Institute of Immunobiology, Fudan University, Shanghai, China.
authors.forename: K
authors.initials: K
authors.lastname: Shao
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Biotherapy Research Center, Institute of Immunobiology, Fudan University, Shanghai, China.|Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Biotherapy Research Center, Institute of Immunobiology, Fudan University, Shanghai, China.|Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Biotherapy Research Center, Institute of Immunobiology, Fudan University, Shanghai, China.|Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Biotherapy Research Center, Institute of Immunobiology, Fudan University, Shanghai, China.|Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Biotherapy Research Center, Institute of Immunobiology, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Ruijin Hospital and Medical School of Shanghai Jiao Tong University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Biotherapy Research Center, Institute of Immunobiology, Fudan University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Biotherapy Research Center, Institute of Immunobiology, Fudan University, Shanghai, China.|Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, China.
authors.forename: G
authors.initials: G
authors.lastname: Liu
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D064591:Allografts / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D065095:Calcineurin Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*; D023001:Transplantation Tolerance / Q000187:drug effects / Q000276:immunology
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus