脂联素及其受体AdipoR1促进血小板生成和免疫耐受干预免疫性血小板减少症的机制研究

免疫耐受失衡和血小板生成减少是免疫性血小板减少症（ITP）疾病发生的关键。我们最近发现，ITP患者Treg比例显著降低，全反式维甲酸治疗可促进Treg比例恢复。项目前期发现，ITP患者脂联素（APN）水平降低，并与血小板计数和Treg比例正相关；APN可促进ITP模型小鼠血小板数量和Treg比例恢复；APN可通过巨核细胞的APN受体AdipoR1抑制肌动蛋白微丝聚合，诱导巨核细胞前血小板形成（PPF）和巨核细胞微粒（MkMPs）产生，且MkMPs可促进Treg分化。鉴此，本项目聚焦的科学问题是：APN及其受体AdipoR1促进血小板生成和免疫耐受干预ITP的机制。我们拟系统研究和明确APN/AdipoR1表达影响ITP疾病的作用规律；揭示APN/AdipoR1调控巨核细胞PPF和Treg分化的分子机制；探索形成以靶向APN/AdipoR1为核心干预ITP的治疗新策略。

Imbalance of immune tolerance and reduced platelet production are the key to the occurrence of immune thrombocytopenia (ITP) disease. We recently found that the proportion of Treg in ITP patients is significantly reduced, and all-trans retinoic acid treatment can promote the recovery of Treg ratio. Our preliminary experiments showed that the level of adiponectin (APN) in ITP patients was reduced and was positively correlated with the platelet count and Treg ratio; APN can promote the recovery of platelet number and Treg ratio in ITP mice model; APN can inhibit actin filaments polymerization through its receptor AdipoR1 on megakaryocytes to induce proplatelet formation (PPF) and megakaryocyte - derived microparticles (MkMPs) release, and MkMPs can promote Treg differentiation in vitro. In view of this, the scientific issue focused on by this project is: the mechanism of APN and its receptor AdipoR1 to promote platelet production and immune tolerance to intervene ITP. We plan to systematically study and clarify the role of APN / AdipoR1 expression affecting ITP diseases; to reveal the molecular mechanism of APN / AdipoR1 regulating the megakaryocyte PPF and differentiation of Treg; to explore the establishing of new therapeutic strategies to intervene ITP by targeting APN / AdipoR1.