Tim-1-Fc suppresses chronic cardiac allograft rejection and vasculopathy by reducing IL-17 production |
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| Authors: | Xiaoming Shi Mingjian Zhang Fang Liu Zhengxing Wang Luding Zhang Haifei Cheng Shu Zhang Teng Fei Meng Guo Jun Bian Quanxing Wang Guoshan Ding |
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| Affiliation: | 1.Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University, Shanghai, China;2.National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China;3.Department of Pharmacology, 411 Naval Medical Hospital, Shanghai, China;4.The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China |
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| 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. |
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| Keywords: | Th17 Tim-1 vasculopathy |
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