黏膜愈合障碍从而诱发与维持肠道炎症是溃疡性结肠炎的重要发病机理，而影响黏膜愈合的具体分子机制不明确。课题组前期研究发现溃疡性结肠炎患者病变黏膜中，IL-34表达水平增加且与肠上皮细胞增殖呈正相关；动物模型中，IL-34基因敲除小鼠对DSS诱导的急性肠炎易感性增高，黏膜愈合延迟，并且，IL-34促黏膜愈合不依赖于巨噬细胞；此外，还发现IL-34通过CSF-1R调控肠上皮细胞周期、提高细胞增殖活力及划痕愈合能力。基于此，与IL-34促进炎症反应加重溃疡性结肠炎的以往认知不同，本申请假设IL-34可能通过CSF-1R促进肠上皮细胞的增殖、加速肠黏膜愈合从而在溃疡性结肠炎中发挥保护作用。本研究拟：1）在大样本中进一步确定IL-34与黏膜愈合在溃疡性结肠炎中的相关性；2）系统阐明IL-34对肠黏膜上皮细胞行为的影响；3）揭示IL-34缓解溃疡性结肠炎的具体分子机制。研究将为疾病治疗提供新思路新靶点。

The pathogenesis of Ulcerative Colitis (UC) remains unclear. Defective and/or delayed mucosal healing has been documented to initiate and maintain gut inflammation. The mechanism of mucosal healing remains to be clarified. Our preliminary experiment showed that IL-34 was remarkably upregulated in the inflamed colonic mucosa in UC patients and was positively correlated with the epithelial cell proliferation status. Animal models demonstrated that IL-34 knockout mice had an increased susceptibility to dextran sulfate sodium-induced acute colitis and delayed mucosal healing. The protective effect of IL-34 was not macrophage-dependent in vivo. The results obtained from cell model in vitro revealed that IL-34 regulated intestinal epithelial cell cycle, improved cell proliferation and facilitated wound healing. Therefore, contrary to previous cognition that IL-34 promotes inflammatory response and aggravates UC, we hypothesized that IL-34 accelerates mucosal healing and functions as a protective role in UC through promoting the proliferation of colonic epithelial cells. We aimed to explore: (1) the relationship between IL-34 and mucosal healing in UC patients; (2) the influence of IL-34 on colonic epithelial cell biological behavior; (3) mechanism of regulating the expression of IL-34 gene in alleviating ulcerative colitis. This project should provide important theoretical basis for the pathogenesis of UC and the molecular mechanism of IL-34 in mucosal healing, and shed a light in finding new drug targets and creating new strategies for promoting mucosal healing.