KGF通过肠上皮源E-cadherin通路参与肠道免疫功能调节作用及其机制的研究

Intestinal intraepithelial lymphocytes (IEL) play important role in maintenance of gastrointestinal immunoregulation and gastrointestinal mucosal barrier, but the specific mechanisms are poorly understood. Integrin CD103 is crucial for the maintenance of number of T cells in gastrointestinal tract and the regulation of migration and homing of T cells. The integrin CD103 functions following binding to E-cadherin (a specific ligand of CD103). It is suggested that cadherin is a key molecule mediating the regulation of number and function of IEL by CD103. Our results found KGF could up-regulate E-cadherin expression in gastrointestinal mucosa of mice. Thus, we speculate that KGF might be involved in the regulation of gastrointestinal immunity via regulating E-cadherin. In vivo and in vitro gastrointestinal I/R models were introduced to the present study, aiming to investigate the effect of KGF on E-cadherin expression in EC and gastrointestinal mucosa and to explore the potential mechanisms. In addition, the influence of KGF on the number, phenotype and function of gastrointestinal IEL was also studied in mice. Our findings may provide evidence supporting the fact that KGF may regulate the gastrointestinal immunity via E-cadherin pathway.

肠上皮间淋巴细胞(IEL)在维持肠道免疫调控和肠粘膜屏障功能中发挥重要作用，但对其调控机制尚缺乏深入的了解。整合素CD103在维持肠道T细胞的数量及调控T细胞的迁移和归巢中起关键作用，其活性作用的发挥依赖于与EC源紧密连接蛋白E-cadherin（特异性配体）的结合，提示E-cadherin是CD103调控IEL数量及功能的关键分子。我们研究发现：KGF可上调小鼠肠道粘膜中E-cadherin的表达，由此我们推测KGF可能通过E-cadherin通路参与肠道免疫调节作用。本课题拟通过体内、体外肠道I/R模型，观察KGF对EC及肠粘膜中E-cadherin表达的调控作用及其调控机制，观察KGF对小鼠肠道IEL数量、表型及功能的调控作用，为阐明KGF可能通过E-cadherin通路参与肠道免疫功能调控提供理论论据。