CD155-TIGIT-MyD88信号在促进血吸虫病肝纤维化中的作用及机制研究

血吸虫病是当前我国乃至世界最严重的寄生虫病之一，每年造成的严重致病、甚至死亡数以万计，其主要原因之一为II型免疫应答介导的宿主肝纤维化所致。迄今，大量研究证明肝脏损伤后可通过复杂的机制诱导以Th2细胞及IL-4为重要代表的显著的II型免疫应答倾向。其成因除血吸虫抗原诱导外，近年研究提示，其中一个重要原因可能在于肝内富集的TIGIT+Treg细胞通过抑制Th1促进Th2细胞分化及效应，但机制并不清楚。文献及我们的前期研究提示，肝脏局部高表达的CD155可能通过激活TIGIT+Treg细胞的TIGIT信号，并通过Myd88信号使TIGIT+Treg细胞扩增并在肝脏内富集，从而参与维持肝脏II型免疫倾向。因此，本课题拟进一步证实上述科学假说，并继续深挖TIGIT信号与Myd88信号的交集机制、以及下游分子机制，为理解肝脏II型免疫倾向的复杂成因及发掘潜在干预措施提供一个新的理论依据。

Schistosomiasis is a chronic helminthic disease that affects approximately 200 million people worldwidely. After Schistosoma japonicum infection, parasite eggs are trapped in host liver and granulomas are induced to form around eggs. Severe granuloma subsequently results in serious liver fibrosis and circulatory impairment chronically. It is important to fully elucidate the mechanisms of the granuloma formation and fibrosis. Previous studies have proven that type II immune response including its typical cytokine IL-4 is one of essential roles for granuloma formation and fibrosis during schistosome infection. However, it remains unclear what factors are involved in facilitating type 2 immune response in the liver. . Although the underline mechanisms are still unknown, recent literatures and our preliminary studies suggest that enrichment of TIGIT+Treg cells in the liver contribute to the type II immune polarization in liver by inhibition of Th1 but facilitating Th2 cell generation. Our preliminary study also suggests that CD155, the ligand of TIGIT, is much higher expressed in the liver than that in spleen and lymph nods. In addition, we also show that MyD88 is probably involved in the expansion of TIGIT+Treg cells in the liver.. In this study, we plan to further confirm that CD155 drives the enrichment of TIGIT+Treg cells in liver by CD155-TIGIT-MyD88 axis to maintain the type 2 immune polarization in liver. In addition, we plan to elucidate the underline molecular mechanisms including the interaction of TIGIT and MyD88 pathway, and the underline signaling after TIGIT-MyD88 activation. Our results will not only be helpful for better understanding the complicate causes of type 2 immune propensity in the liver fibrosis in schistosomiasis, but also provide potential targets for the interventions of liver fibrosis-associated diseases.