Tim-3/Gal-9信号通路在间充质干细胞中减轻急性移植物抗宿主病治疗中的研究进展

Research Progress of Tim-3/Gal-9 Signaling Pathway in the Treatment of Acute Graft-Versus-Host Disease in Mesenchymal Stem Cells

移植物抗宿主病(Graft versus Host Disease, GvHD)是异基因造血干细胞移植(allo-HSCT)后的严重并发症。急性GvHD (aGVHD)发生于同种异体造血干细胞移植后,受体的组织抗原被表达给供体T细胞,从而导致供体T细胞激活、表达,增强对宿主的免疫反应,攻击健康的受体组织。aGVHD的发生率约为30%~50%。aGVHD的初始治疗是类固醇。对类固醇没有反应的aGVHD患者的预后很差。间充质干细胞(mesenchymal stem cells, MSCs)因其具有调节免疫特性,在aGVHD的治疗中显示相当大的前景。MSCs表达的β-半乳糖苷结合凝集素-9 (Galectin-9, Gal-9)是免疫抑制的重要调节因子,通过与T细胞免疫球蛋白及黏蛋白结构域分子(T-cell immunoglobin mucin-3, Tim-3)结合,发挥免疫调控作用,在调节T细胞亚群及免疫耐受中起着重要作用。在移植后早期增强Tim-3/Gal-9途径的信号传导以抑制免疫应答,调节T细胞增殖,改善致死率,可成为异基因造血干细胞移植后免疫调节新途径。

Graft versus host disease (GvHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Acute GvHD (aGVHD) occurs after allogeneic hematopoietic stem cell transplantation. The tissue antigen of the recipient is expressed to the donor T cells, resulting in the activation and expression of the donor T cells, enhancing the immune response to the host, and at-tacking the healthy recipient tissue. The incidence of aGVHD is about 30%~50%. The initial treat-ment of aGVHD is steroids. The prognosis of aGVHD patients who did not respond to steroids was poor. Mesenchymal stem cells (MSCs) have great prospects in the treatment of aGVHD due to their immunomodulatory properties. MSCs expressed β-Galactin-9 (Gal-9) is an important regulator of immunosuppression. It plays an important role in immune regulation by combining with T-cell immunoglobulin and mucin domain molecule (Tim-3). Enhancing the signal transduction of Tim-3/Gal-9 pathway in the early stage after transplantation can inhibit the immune response, reg-ulate the proliferation of T cells, and improve the mortality rate, which can become a new way of immune regulation after allogeneic hematopoietic stem cell transplantation.