TREM-2是新近发现的模式识别受体，然而其在眼免疫中的功能仍不清楚。预实验结果显示，细菌感染小鼠角膜诱导TREM-2表达，提示TREM-2可能与角膜免疫相关。沉默了TREM-2的小鼠角膜的细菌量和炎症因子表达上调，疾病加重，提示TREM-2参与角膜保护。那么，TREM-2介导角膜保护的分子机制如何？进一步实验发现，TREM-2的抑炎作用依赖于β-catenin。目前TREM-2的配体及下游信号通路仍不明确，结合文献报道和预实验结果，我们首次提出"TREM-2通过结合内源性配体HSP60激活β-catenin通路，进而促进细菌清除、抑制过度炎症，保护角膜"的假说。本项目拟通过抗体交联活化和RNA干扰沉默等动物模型及体外实验，从正、反两方面揭示TREM-2介导的角膜保护作用及其机制，确定在角膜炎中，TREM-2的关键配体及其激活β-catenin的分子机制，为细菌性角膜炎的防治提供理论依据。

Triggering receptors expressed on myeloid cells 2(TREM-2) is a new pattern recognition receptor, however, the role of TREM-2 in ocular immunity remains unclear. Our preliminary data showed that, bacterial infection induced TREM-2 expression in the mouse cornea, indicating that TREM-2 may participate in the ocular immune response. Moreover, we found that silencing of TREM-2 accelerated the disease progression and enhanced the viable bacterial number as well as pro-inflammaoty cytokine expression in the mouse cornea, suggesting that TREM-2 plays a protective role at the ocular surface. Next question is to explore the molecular mechanism of TREM-2 mediated corneal protection. Our preliminary data further demonstrated that the anti-inflammatory activity of TREM-2 is β-catenin-dependent. Although little is known regarding the specific ligand and downstream signaling of TREM-2, based on the literature and our preliminary data, we hypothesize that TREM-2 activates β-catenin signaling pathway by binding to its endogenous ligand heat shock protein 60 (HSP60), and protects the cornea by promoting bacterial clearance and by suppressing inflammtory response. This project will use different murine models of Pseudomonas aeruginosa keratitis to test the role of TREM-2 in bacterial keratitis and to explore the mechanism of TREM-2 mediated immune regulation. Furthermore, we will identify the molecular mechanism by which TREM-2 induced the activation of β-catenin. This project will provide substantive information for prevention and clinical treatment of bacterial keratitis.