title: Tim-1-Fc suppresses chronic cardiac allograft rejection and vasculopathy by reducing IL-17 production.
abstract: Previously, we demonstrated that Tim-1-Fc prevents acute cardiac graft rejection by inhibiting Th1 response. In the present report, we tackled the impact of Tim-1-Fc on Th17 cells in a model of cardiac chronic rejection. Administration of Tim-1-Fc did not result in a detectable impact on innate immunity and regulatory T cells, while it provided protection for Bm12-derive cardiac grafts against chronic rejection in B6 recipients, as manifested by the reduction of inflammatory infiltration along with less severity of vasculopathy. Studies in T-bet(-/-) recipients by implanting Bm12-derived cardiac grafts further revealed that Tim-1-Fc significantly protected cardiac grafts from chronic rejection along with attenuated production of IL-17 producing T cells. Depletion of CD4 and CD8 T cells or blockade of IL-17 in T-bet(-/-) recipients demonstrated that Tim-1-Fc selectively suppresses Th17 differentiation along with attenuated IL-17 secretion. Together, our data suggest that Tim-1-Fc protects cardiac grafts from chronic rejection by suppressing CD4 Th17 development and functionality. Therefore, Tim-1-Fc might be a potential immunosuppressive agent in the setting of cardiac transplantation.
authors.affiliation: Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Shi
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University Shanghai, China.
authors.forename: Mingjian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Luding
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, 411 Naval Medical Hospital Shanghai, China.
authors.forename: Haifei
authors.initials: H
authors.lastname: Cheng
authors.affiliation: The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Fei
authors.affiliation: Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, 411 Naval Medical Hospital Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Bian
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University Shanghai, China.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University Shanghai, China.
authors.forename: Guoshan
authors.initials: G
authors.lastname: Ding
mesh_terms: D064591:Allografts; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D018920:Coculture Techniques; D004195:Disease Models, Animal; D015536:Down-Regulation; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D000072596:Hepatitis A Virus Cellular Receptor 1; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D000098815:T-bet Transcription Factor
chemical_list: C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; C098680:Il17a protein, mouse; D007141:Immunoglobulin Fc Fragments; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D008565:Membrane Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Th17; Tim-1; vasculopathy