根尖周炎骨破坏与免疫状态密切相关。淋巴细胞活化基因-3（LAG-3）是重要的负性免疫检查点分子。本课题组前期研究发现LAG-3在人根尖周炎CD4+T细胞表达。由此提出科学假说：“LAG-3通过调节根尖周免疫微环境抑制根尖周炎骨破坏”。本项目从LAG-3对T细胞及Treg细胞功能调控入手，拟研究：(1)明确LAG-3在根尖周炎T细胞及Treg细胞上的表达与骨破坏之间的关系；（2）建立小鼠实验性根尖周炎模型，抗体阻断LAG-3，明确其对根尖周炎骨破坏的作用；（3）构建LAG-3基因敲除小鼠实验性根尖周炎模型，流式分选T细胞及Treg细胞，明确LAG-3通过抑制T细胞活化影响破骨细胞分化及功能，以及LAG-3通过增强Treg细胞免疫调节功能，导致T细胞失能，抑制炎性破骨。进一步体内回输LAG-3高表达Treg细胞观察可否挽救骨破坏的表型。本项目的开展将加深对根尖周炎骨破坏的免疫调节机制的理解。

Bone destruction of periapical lesions is critically related to inflammatory immune response. Lymphocyte activation gene-3 (LAG-3) is one of the most important immune checkpoint molecules. Our pilot study verified that LAG-3 significantly increased on CD4+T cells within periapical lesions. Thus we hypothesize that LAG-3 suppressed inflammatory bone loss of periapical lesions through modulating immune microenvironment. This project includes three parts: Firstly, we plan to quantify the expression of LAG-3 on CD4+T cell and regulatory T cell (Treg cell) within human periapical lesion specimen, then we will analyse the correlation of LAG-3 expression with the degrees of periapical bone loss. Secondly, we intend to generate experimental mouse model of periapical lesion. We plan to further block LAG-3 using monoclone antibody to investigate its in vivo function. Thirdly, we intend to generate experimental mouse model of periapical lesion using LAG-3 knock out mice. For investigating molecular mechanism of LAG-3 in modulating inflammatory bone loss, we plan to sort out T cells and Treg cells by flow cytometry and generate ex vivo experiments. The adoptive transfer of LAG-3+ Tregs to LAG-3 knock out mice will be performed to verify the alleviation of inflammatory osteolysis. Achievements of this project will contribute to a better understanding of the mechanism of immune checkpoint molecule LAG-3 in regulating periapical bone loss.