器官移植是器官衰竭患者最有效、甚至唯一的外科治疗手段，主要障碍是移植排异反应。探索调控宿主免疫应答机制、开发免疫治疗策略是器官移植领域的研究重点。巨噬细胞M2型极化可诱导免疫耐受，其调节机制研究在肿瘤、自身免疫病、移植排斥等领域具有良好的临床应用前景。共刺激分子CD155对巨噬细胞极化发挥独特的调控效应。本课题组从事CD226-CD155结构与功能研究，发现阻断其相互作用可以抑制免疫反应。CD226抗体和/或TIGIT重组蛋白促进巨噬细胞M2型极化、诱导Treg细胞分化，抑制小鼠移植排异反应，延长移植物存活时间。本课题拟深入探讨同种异体移植排斥反应中，CD226/TIGIT竞争性结合CD155、调控巨噬细胞极化和功能的效应；阐明CD155促进M2型极化、进而诱导Treg细胞分化的机制，有望加深和拓展这一重要共刺激分子与巨噬细胞功能调控的认识，为移植排斥机制研究和免疫治疗提供新思路。

Organ transplantation is the most effective or even the only surgical treatment for patients with organ failure. The main obstacle is transplantation rejection. Exploring the mechanism of host immune responses regulation and developing immunotherapeutic strategies are the research focuses in the field of organ transplantation. Macrophage M2 polarization can induce immune tolerance, and its regulation mechanism has good clinical application prospects in the fields of tumor, autoimmune disease, and transplant rejection. The co-stimulatory molecule CD155 exerts a unique regulatory effect on macrophage polarization. Our group is engaged in the study of the structure and function of CD226-CD155 and found that blocking its interaction can inhibit the immune response. The CD226 antibody and/or TIGIT recombinant protein promotes macrophage M2 polarization, induces Treg cell differentiation, inhibits transplantation rejection in mice, and prolongs graft survival. This research is intend to investigate the mechanism of CD226/TIGIT competitive binding to CD155, the effects of CD226/TIGIT in regulation of macrophage polarization and its function in allograft rejection, to elucidate the mechanism by which CD155 promotes M2 polarization and thereby induces Treg cell differentiation, thus to expand the understanding of this important co-stimulatory molecule in macrophage function regulation, provide new ideas for the study of transplant rejection mechanism and immunotherapy.