FGL2调节炎症性肠病肠道免疫平衡的分子机制

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic inflammatory diseases. Despite great efforts to understand the etiology of IBD and to improve treatment, IBD will remain a major health concern for the gastrointestinal community for the foreseeable future. The ability to maintain the epithelial barrier integrity is critical in protecting host from a hostile environment in the intestinal lumen. Dysregulation of immune responses plays a critical role in the disease progression of IBD. It has been shown that excessive proliferation of the cytotoxic T cells (CTLs), reduced number of regulator T cells (Tregs) or dysfunction of Tregs are associated with the intestinal mucosa injury. Recent studies identified that Tregs-secreted soluble fibrinogen-like protein (aFGL2) had immunosuppressive effects. It can inhibit DC maturation, induce B cell apoptosis, and attenuate T cell proliferation. Our recent studies indicated that the expression levels of sFGL2 was significantly increased in IBD patients and were correlated to the disease severity. However, the role of sFGL2 in regulating immune response and modulating disease progression of IBD remains to be determined. The major objective of this study is to examine the role of sFGL2 in regulating immune response in the intestinal tract and further identify the underlying mechanisms using sFGL2+/+ and sFGL2-/- IBD mouse models. Furthermore establish the basis for IBD's diagnose and therapy.

炎症性肠病（IBD）是一种慢性非特异性肠道炎症性疾病，其中免疫调节异常是其发病的重要因素。效应T细胞过度增殖，Treg细胞数量减少或功能异常，均可打破肠道内免疫平衡，从而导致肠黏膜损伤，诱导IBD发生。近来的免疫学研究证实，分泌型纤维蛋白原样蛋白-2（sFGL2）是Treg细胞分泌的效应分子，通过抑制树突状细胞（DC）成熟，诱导B细胞凋亡，从而导致效应T细胞增殖及免疫活性减弱，最终发挥免疫抑制作用。我们以往的研究发现在人的IBD肠道组织中sFGL2的表达升高。我们提出假设：sFGL2作为Treg细胞的效应分子，发挥免疫调节活性抑制IBD的进展。为此，我们采用FGL2+/+ IBD小鼠和基因敲除后的FGL2-/- IBD小鼠模型，观察在sFGL2调节肠道免疫平衡的作用，并探讨相关的机制。为IBD的临床诊治奠定基础。