Galectin-9 is required for endometrial regenerative cells to induce long-term cardiac allograft survival in mice
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RESEARCH
Open Access
Galectin-9 is required for endometrial regenerative cells to induce long-term cardiac allograft survival in mice Yiming Zhao1,2,3†, Xiang Li1,2†, Dingding Yu1,2, Yonghao Hu1,2, Wang Jin1,2, Yafei Qin1,2, Dejun Kong1,2, Hongda Wang1,2, Guangming Li1,2, Alessandro Alessandrini3 and Hao Wang1,2*
Abstract Background: Endometrial regenerative cells (ERCs), a novel type of mesenchymal-like stem cells, were identified as an attractive candidate for immunoregulation and induction of cardiac allograft tolerance. However, the underlying mechanisms of ERCs in immune regulation still remain largely unclear. The present study is designed to determine whether the expression of Galectin-9 (Gal-9), a soluble tandem-repeat member of the galectin family, is crucial for ERC-based immunomodulation. Methods: In this study, we measured Gal-9 expression on ERCs and then co-cultured Gal-9-ERCs, ERCs, and ERCs+lactose (Gal-9 blocker) with activated C57BL/6-derived splenocytes. Furthermore, we performed mouse heart transplantation between BALB/c (H-2d) donor and C57BL/6 (H-2b) recipient. ERCs were administrated 24 h after the surgery, either alone or in combination with rapamycin. Results: Our data demonstrate that ERCs express Gal-9, and this expression is increased by IFN-γ stimulation in a dosedependent manner. Moreover, both in vitro and in vivo results show that Gal-9-ERC-mediated therapy significantly suppressed Th1 and Th17 cell response, inhibited CD8+ T cell proliferation, abrogated B cell activation, decreased donorspecific antibody production, and enhanced the Treg population. The therapeutic effect of ERCs was further verified by their roles in prolonging cardiac allograft survival and alleviating graft pathological changes. Conclusions: Taken together, these data indicate that Gal-9 is required for ERC-mediated immunomodulation and prevention of allograft rejection. Keywords: Endometrial regenerative cells, Cardiac allograft rejection, Galectin-9, Immunoregulation, Rapamycin
Background Organ transplantation is an effective substitute and supportive treatment for tumor, irreversible organ damage, and end-stage organ failure [1, 2]. The diversity of individual major histocompatibility complex (MHC) greatly restricts * Correspondence: [email protected] † Yiming Zhao and Xiang Li contributed equally to this work. 1 Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China 2 Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China Full list of author information is available at the end of the article
the survival of organ transplants [3]. Thankfully, in recent years, with the application of immunosuppressants, shortterm allograft survival rate has greatly improved, whereas cardiac allograft vasculopathy (CAV) caused by chronic rejection still affects the long-term survival of the transplanted organs [4]. Meanwhile, for the recipients, the side effects of longterm and high-dose use of immunosu
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