凋亡细胞被吞噬细胞及时有效清除是免疫耐受微环境形成的重要条件。项目组前期发现：Kupffer细胞（KCs）是肝内主要吞噬细胞，其介导的T细胞凋亡是肝移植免疫耐受形成的重要原因；但当凋亡细胞超过KCs清除能力时，则会诱导排斥反应。新近发现清道夫受体F类成员1（SCARF1）在调控凋亡细胞清除，释放免疫抑制因子，诱导免疫耐受微环境形成中发挥关键作用；且其调控作用强于既往发现的“噬我”分子。但相关研究主要集中在自身免疫性疾病方面，尚未涉及移植领域，更未涉及KCs。我们认为该分子在KCs介导的凋亡细胞清除及诱导肝移植免疫耐受中也起重要作用。因此，本项目选择肝KCs为靶细胞，以SCARF1为切入点，分离KCs并建立肝移植模型，采用基因敲除、敲入及纳米技术，沉默或增强SCARF1表达，探讨SCARF1在KCs介导的凋亡细胞清除中的作用及相关分子机制，阐明该分子在诱导移植肝脏免疫耐受形成中的作用机制。

The prompt removal of apoptotic cells by phagocytes is important for immune tolerance induction. Kupffer cells (KCs), the most important resident phagocytes of the liver, comprise one of the major population of the hepatic nonparenchymal cell fraction, and the tolerogenic properties of the liver are generally accepted. Therefore increased attention has focused on the possible role and mechanism of KCs from liver allograft in tolerance induction. Over a decade of research, our group demonstrated that KCs induced antigen-specific T cell apoptosis is crucial for promoting immune tolerance formation, but we don’t how apoptotic T cells are cleared in liver after transplantation. A recent study reported that scavenger receptor class F member 1 (SCARF1) plays a pivotal role in apoptotic cells clearence and the molecule shows more powerful engulfment ability than other “eat-me” molecules (such as MFG-E8, CD91, Tim-3, Tim-4, et al). But so far there is no related research in solid organ transplantation, especially in liver. We hereby put forward a hypothesis that up-regulation of SCARF1 in KCs may induce liver transplant tolerance via enhancing antigen-specific apoptotic T cells clearance and immunosuppressive cytokines secretion. To clarify the role of the molecule in liver tolerance induction, we will separate KCs and establish liver transplantation model in mice, using SCARF1 gene knock-in or knock-out mice to enhance or inhibit SCARF1 expression both in vitro and in vivo. Once the hypothesis of up-regulation of SCARF1 in KCs mediating the self-tolerance induction in liver transplantation is corroborated, this molecule can become a novel target for treatment of acute rejection.