血小板αIIb启动子控制卵白蛋白（OVA）靶向诱导抗原特异性免疫耐受及机制的研究

诱导自身或异体靶抗原的特异性免疫耐受可以治疗自身免疫性疾病或器官移植排斥反应。我们课题组报道了血小板αIIb启动子控制凝血因子可使凝血因子储存于小鼠血小板的α颗粒内，并诱导了小鼠对凝血因子产生特异性免疫耐受。但是自身或异体靶抗原多数是非凝血蛋白，而目前尚不明确该启动子控制非凝血蛋白是否也可诱导对非凝血蛋白产生特异性免疫耐受，也未阐明这种诱导免疫耐受的机制。我们前期研究用卵白蛋白（OVA）这种非凝血蛋白来代替靶抗原，发现αIIb启动子控制OVA也可使OVA蛋白储存于小鼠血小板的α颗粒内。本项目将在此基础上，通过研究血小板αIIb启动子控制OVA是否可诱导小鼠对OVA产生特异性免疫耐受，以及OVA特异性CD4+T细胞、Treg细胞等免疫细胞与血小板在这种诱导免疫耐受中的相互作用机制，为今后利用αIIb启动子控制靶抗原诱导靶抗原特异性免疫耐受，治疗自身免疫性疾病或器官移植排斥反应提供理论依据。

Induction of autoantigen or alloantigen-specific immune tolerance is a desirable therapy for autoimmune diseases or organ transplantation rejection. Our research group have demonstrated that targeting coagulant protein expression to platelets under control of the platelet-specific αIIb promoter can not only results in coagulant protein storage in platelet α-granules, but also induce coagulant protein-specific immune tolerance in hemophilia mice. However, most of autoantigens or alloantigens in autoimmune diseases or organ transplantation rejection are non-coagulant proteins, whether targeting non-coagulant proteins expression to platelets under control of the platelet-specific αIIb promoter can induce immune tolerance to non-coagulant proteins is still unknown, and the mechanism of this induced immune tolerance is also unexplored. In our preliminary experiment we used ovalbumin(OVA) that is a non-coagulant protein to replace autoantigen or alloantigen，data showed that targeting OVA expression to platelets under control of the platelet-specific αIIb promoter can also result in OVA storage in mouse platelet α-granules. In this study, based on the data and mouse model, we are going to explore whether targeting OVA expression to platelets under control of the platelet-specific αIIb promoter can induce OVA-specific immune tolerance, and study the interaction mechanisms between immune cells (OVA specific CD4+ T cell, Treg cell, etc) and platelets in this induced immune tolerance. This research will provide the theories for treatment of autoimmune diseases or organ transplantation rejection through the induction of autoantigen or alloantigen-specific immune tolerance by targeting autoantigen or alloantigen expression to platelets under control of the platelet-specific αIIb promote.