MHCⅡ-LAG3信号调控Treg分化在泡型包虫病发病中的机制研究

泡型包虫病（AE）是新疆、青海等西部地区高发人畜共患病，俗称“虫癌”，至今无有效治疗手段。AE患者临床表现与机体免疫抑制状态密切相关，而Treg是诱导免疫抑制形成的重要因素。我们前期发现负性免疫检查点LAG3在AE患者肝脏局部和外周CD4+T细胞表面呈高表达，导致免疫功能降低，参与Treg细胞的分化。此外，其配体MHCⅡ主要定位在B细胞表面，提示B细胞通过MHCⅡ-LAG3信号诱导Treg分化，但具体机制不明。本项目拟利用临床标本，明确LAG3及其配体MHCⅡ在诱导AE患者Treg分化中作用，与临床特征的相关性；建立小鼠模型（野生型和缺陷型），阐明B细胞通过MHCⅡ-LAG3信号调控Treg细胞分化的分子机制；靶向阻断MHCⅡ-LAG3信号或细胞转输，以证实抑制Treg分化，恢复效应T细胞免疫功能，用于AE治疗的可行性和有效性，为探讨包虫病新的免疫治疗方法提供重要依据。

Vesicular echinococcosis (AE) is a high incidence zoonosis in Xinjiang, Qinghai and other western regions, commonly known as "worm cancer", so far there is no effective treatment. The clinical manifestations of AE patients are closely related to the state of immunosuppression, and Treg is an important factor inducing the formation of immunosuppression. We previously found that Lag3 was highly expressed on the surface of CD4+T cells in the liver and peripheral of AE patients, which led to the decrease of immune function and involved in the differentiation of Treg cells. In addition, MHCⅡ is mainly located on the surface of B cells, suggesting that B cells can induce Treg differentiation by MHCⅡ-Lag3 signal, but the specific mechanism is unknown. This project intends to use clinical samples to clarify the role of Lag3 and its ligand MHCⅡin inducing Treg differentiation in AE patients, and the correlation with clinical characteristics; Mice model (wild type and defective type), clarify the molecular mechanism of B cell regulating Treg cell differentiation through MHCⅡ-Lag3 signal; target to block MHCⅡ-Lag3 signal or cell transfer, so as to confirm the inhibition of Treg differentiation and recovery effect of T cells Immune function, used for the feasibility and effectiveness of AE treatment, provides an important basis for the study of new immunotherapy of echinococcosis.