LAIR-1在幽门螺杆菌逃逸宿主免疫应答中的作用研究

幽门螺杆菌(H.pylori)可逃逸宿主免疫应答，但其机制尚未明确。新发现的免疫抑制性分子LAIR-1可与胶原(H.pylori的高亲和力配体)特异性结合并发生聚集，聚集后的LAIR-1通过胞浆区两个ITIM基序募集SHP-1而抑制效应细胞激活信号的转导。我们前期研究发现，H.pylori与U937细胞相互作用可导致后者LAIR-1的分泌增加，并且LAIR-1的表达水平随着H.pylori与细胞比例的增加而有所升高。本项目拟在前期研究基础上，采用ELISA、RT-PCR、Western Blot、流式细胞术等技术研究H.pylori对LAIR-1分子在单核细胞、胃黏膜上皮细胞中表达的影响；通过RNA干扰、细胞转染及靶向阻断信号通路等方法研究LAIR-1募集SHP-1参与的相关信号通路，以期阐明H.pylori逃逸宿主免疫应答的新机制，为H.pylori感染的防治提供新思路。

Helicobacter pylori (H. pylori) can escape the host immune response, but the mechanism has not been clarified. The newly discovered molecular LAIR-1 can specifically combine with collagen, the high affinity ligand of H. pylori and then can be coaggregated on the cell surface. LAIR-1 could recruits SHP-1 through its two ITIM motif in the cytoplasmic region and inhibits the transduction of the downstream activating signals in effect cells, thus inhibit the immune system. Our preliminary results show that H. pylori cocultured with U937 cells may lead to an increase secretion of LAIR-1 and with the increasing ratio between H. pylori and cells, the expression of LAIR-1 raised. This project is intended to use ELISA, RT-PCR, Western Blot and Flow Cytometry to study the influence of H. pylori on the expression of LAIR-1 on monocytes. Then, use siRNA, cell transfection and targeted signal pathway blocking method, to investigate the role of LAIR-1 in the immune escape of H. pylori and related signal pathways with the participation of SHP-1. The project is going to clarify a novel mechanism of H. pylori how to escape the host immune response and provide a new idea for the prevention of H. pylori infection.