肠黏膜屏障（IMB）是机体防御的重要屏障。肠上皮下成纤维细胞(ISEFs)与肠上皮细胞（IEC）之间可通过crosstalk调节IMB功能。在前一课题里我们验证了ISEFs对IMB功能的保护作用,并发现内源性抗菌肽LL-37在ISEFs对IMB的调控作用中扮演着重要角色，但机制尚不完全明确。近来研究发现, LL-37可通过上调IL-36促进组织的损伤修复，据此我们推测LL-37可通过诱导肠上皮源性IL-36的表达作用于ISEFs表面IL-36受体(IL-36R),激活ISEFs分泌KGF、TGF-β等细胞因子对肠屏障的保护促进。因此，本项目拟通过ISEFs–IEC共培养模型及小鼠IMB损伤模型，提出LL-37-IL-36 axis通路是ISEFs调节IMB的关键通路，为深入阐明ISEFs-IEC crosstalk机制在病理条件下对IEB的调控提供理论依据，筛选肠黏膜损伤保护的干预新靶点。

Intestinal mucosa barrier (IMB) is an important barrier to the body's defense. Intestinal epithelium of fibroblasts (ISEFs) -intestinal epithelial cells (IEC) crosstalk has been shown to be closely involved in the regulation of intestinal epithelial barrier function. Our previous studies have shown that the ISEFs play a protective role in IMB function, and found that endogenous antimicrobial peptides LL-37 plays an important role in regulation of IMB, the mechanism of this regulation has not been well understood. Several lines of evidence suggested that LL-37 can promote tissue damage repair by IL-36 upregulation, according to that we assum that LL-37 can promote IEC-derived IL-36 expression,the later binding to ISEFs surface IL-36 receptor (IL-36R), activating ISEFs secrete protective cytokine such as KGF, TGF-β to protect the intestinal epithelial barrier.In this study, we put forward the LL-37-IL-36 axis is considered to be the key pathway to regulate the intestinal barrier function by ISEFs-IEC co-culture system and necessary animal model. This proposal would give insight into the mechanism of ISEFs-IEC crosstalk in maintaining intestinal barrier homeostasis and may provide novel strategy to prevent the loss of intestinal barrier function. To further clarify ISEFs-IEC crosstalk mechanism under the condition of the pathology of IMB regulation provides theoretical basis for screening of intestinal mucosa damage protection of new targets for intervention.