Galectin-1 Prolongs Survival of Mouse Liver Allografts From Flt3L-Pretreated Donors

Authors

  • Y. Ye,

    1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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    • Both authors contributed equally to this work.

  • S. Yan,

    1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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    • Both authors contributed equally to this work.

  • G. Jiang,

    1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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  • L. Zhou,

    1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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  • H. Xie,

    1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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  • X. Xie,

    1. Department of General Surgery, Division of Gastrointestinal Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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  • X. Yu,

    1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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  • Y. Ding,

    1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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  • J. Tian,

    1. Department of Nephrology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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  • Y. Dai,

    1. The Center of Metabolic Disease Research, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China
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  • S. Zheng

    Corresponding author
    • Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Corresponding author: Shusen Zheng

shusenzheng@zju.edu.cn

Abstract

Liver allografts are spontaneously accepted across MHC barriers in mice. The mechanisms underlying this phenomenon remain poorly understood. Galectin-1, an endogenous lectin expressed in lymphoid organs, plays a vital role in maintaining central and peripheral tolerance. This study was to investigate the role of galectin-1 in spontaneous tolerance of liver allografts in mice, and to evaluate the therapeutic effects of galectin-1 on liver allograft rejection induced by donor Flt3L pretreatment. Blockade of the galectin-1 pathway via neutralizing antigalectin-1 mAb did not affect survival of the liver allografts from B6 donors into C3H recipients. Administration of rGal-1 significantly prolonged survival of liver allografts from Flt3L-pretreated donors and ameliorated Flt3L-triggered liver allograft rejection. This effect was associated with increased apoptosis of T cells in both allografts and spleens, decreased frequencies of Th1 and Th17 cells, decreased expression of Th1-associated cytokines (IL-12, IL-2 and IFN-γ), Th17-associated cytokines (IL-23 and IL-17) and granzyme B, in parallel with selectively increased IL-10 expression in liver allografts. In vitro, galectin-1 inhibited Flt3L-differentiated DC-mediated proliferation of allo-CD4+ T cells and production of IFN-γ and IL-17. These data provide new evidence of the potential regulatory effects of galectin-1 in alloimmune responses in a murine model of liver transplantation.

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