TSLP激活树突状细胞介导Trm细胞异常分化、活化在特应性皮炎发生发展中的作用及机制研究

特应性皮炎（Atopic Dermatitis, AD）是一种以T细胞介导为主的复发性慢性炎症性皮肤病。然而，循环中T细胞的异常不能完全阐明AD的发生和迁延不愈。组织原位型记忆T细胞（Trm）是新近发现的T细胞亚型，参与多种炎症性皮肤病。我们前期工作发现AD患者皮损中Trm数量增多；再者，我们亦观察到OVA诱导AD小鼠模型中皮损中Trm表达水平增高，提示Trm细胞可能参与AD的发生发展。已有研究发现AD异常高表达TSLP且TSLP可以直接被树突状细胞提呈，病毒感染模型提示不同亚型的树突状细胞能不同程度影响Trm细胞的启动、分化和活化，然而AD中树突状细胞如何激活Trm细胞暂无报道。因此我们假设：TSLP调控树突状细胞，介导Trm细胞分化活化进而参与AD的发生与复发。本课题拟从体内体外实验探究AD中Trm细胞异常分化活化的具体机制，为寻找AD治疗新靶点提供理论依据。

Atopic Dermatitis (AD) is a recurrent chronic inflammatory skin disease mediated by T cells. However, these abnormal circulating T cells can’t fully explain the relapse of AD. Tissue resident memory T cells (Trm cells) are a newly identified T cells subtype, which involved in various inflammatory skin diseases. Our previous work found that the increased number of Trm cells in AD patients’ skin lesions; in addition, we also observed that increased Trm cells in skin lesions of OVA-induced AD mouse models, suggesting that Trm cells may participate in the development of AD. Studies have proved abnormal expression level of TSLP in AD and TSLP can be directly presented by dendritic cells. Virus infection models suggest that different subtypes of dendritic cells can affect the initiation, differentiation and activation of Trm cells. However, the mechanism behind dendritic cells activate Trm cells in AD has not been reported yet. Therefore, we hypothesize that TSLP primes dendritic cells, mediates the differentiation and activation of Trm cells, which participate in the occurrence and relapse of AD. This project intends to explore the specific mechanism of abnormal differentiation and activation of Trm cells in AD by in vivo and in vitro experiments, and provide a theoretical basis for finding novel therapeutic targets for AD.