C型凝集素受体LSEtin在实验性结肠炎组织修复中的功能研究

Ulcerative colitis (UC) is a chronic gastrointestinal disorder, and the incidence of UC is increased year by year at home and abroad. Immune response plays an important role in the development of UC. In addition to host defence, immune response triggers tissue regeneration and repair. Whereas host defence has been extensively studied, the mechanisms by which immune response stimulates regenerative responses remain obscure. LSECtin (liver node sinusoidal endothelial cell lectin) is a C-type lectin receptor and expressed in intestinal macrophage. Our preliminary data show that LSECtin alleviates experimental colitis through phenotype analysis of LSECtin+/+ and LSECtin-/- colitis mice induced by DSS. Interestingly, intestinal macrophages from LSECtin+/+ colitis mice secrete more growth factors and promote tissue proliferation, compared with LSECtin-/- colitis mice. These results lead us to propose that in the experimental colitis LSECtin accelerates the process of tissue regenerative and repair responses through the induction of growth factors and results in the alleviation of experimental colitis. Thus, this project can help us understand the role of intestinal macrophages in the regenerative and repair responses.

溃疡性结肠炎（ulcerative colitis, UC）是一种慢性肠道疾病，在国内外的发病率都呈现逐年上升的趋势。肠道免疫反应在UC发生发展中发挥重要作用。除了其在保护机体免受病原微生物的感染中发挥作用，免疫反应也参与肠道组织再生与修复。关于免疫反应介导宿主防护中的作用已有大量研究，但是其在组织修复中的作用机制仍不清楚。LSECtin是C型凝集素受体分子，表达在肠道巨噬细胞。通过比较LSECtin野生型和敲除型肠炎小鼠的表型，我们的初步研究结果显示LSECtin能够减缓实验性结肠炎的发生。进一步研究发现表达LSECtin的巨噬细胞分泌更多的生长因子，并促进肠道组织细胞的增殖。这些结果引导我们提出这样一个假设，即在肠炎发生过程中LSECtin会促进巨噬细胞分泌更多的生长因子从而促进肠道上皮细胞的修复进而减缓肠炎发生。因此本研究有助于人们理解肠道巨噬细胞在组织修复中的作用机制。

上皮细胞损伤是炎性肠疾病的主要原因。然而，肠上皮稳态调控的细胞和分子机制仍不清楚。我们的研究显示巨噬细胞上的C型凝集素受体LSECtin（Clec4g）在葡聚糖硫酸钠（Dextran sodium sulfate，DSS）诱导的小鼠实验性肠炎模型中发挥保护作用。具体的机制是LSECtin能够促进巨噬细胞对肠道凋亡细胞的清除，进而使巨噬细胞分泌更多的生长因子来促进肠道粘膜的修复。LSECtin的缺失导致结肠巨噬细胞吞噬紊乱和肠上皮修复受损。总之，我们的研究结果表明，LSECtin在促进巨噬细胞对凋亡细胞的清除后能够分泌更多的生长因子从而加快受损肠道粘膜的修复。