AhR调控IEL-IEC crosstalk在维护肠黏膜稳态中的作用及机制研究

肠上皮间淋巴细胞（IEL）是肠道免疫系统参与肠上皮细胞（IEC）互动的重要细胞，IEL-IEC crosstalk机制在肠黏膜屏障（IEB）稳态维持中发挥重要作用。我们前期研究显示：IEL源KGF与IEC源IL-7在该机制中扮演重要角色，但其调控机制仍需进一步阐明。研究表明，芳香烃受体（AhR）是协调IEL-IEC crosstalk，维持肠黏膜稳态的关键连接点；另有证据提示：AhR还可能通过调控IL-7及KGF在IEL-IEC crosstalk中发挥重要作用，并参与多个IEL及IEC源细胞因子的调控。为此，本课题拟观察AhR在IEB稳态维持中的作用及对IEL表型和功能的影响，研究IL-7及KGF在AhR调控 IEL-IEC crosstalk中的作用，明确IEL源细胞因子在AhR调控IEB功能中的作用及机制。阐明AhR在维护IEB稳态中的关键作用，为IEB保护提供新策略。

Intestinal intraepithelial lymphocytes (IELs) play an important role in the interaction between intestinal epithelial cells (IECs) and gut immune cells. The crosstalk between IELs and IECs has been shown to be closely involved in the regulation of intestinal barrier homeostasis. Our previous studies have shown that both IEL-derived keratinocyte growth factor (KGF) and IEC-derived IL-7 play important roles in this crosstalk; however, the mechanism of this regulation has not been well understood. It has been shown that aryl hydrocarbon receptor (AhR) could regulate IEL-IEC crosstalk in the maintenance of intestinal barrier homeostasis. Several lines of evidence suggested that AhR could regulate IL-7 and KGF expression, as well as other cytokines from IELs or IECs. We hypothesize that AhR is a key transcription factor linking IEL-IEC crosstalk to the intestinal barrier homeostasis. In this study, we will investigate the role of AhR in the maintenance of intestinal barrier function. The changes of IEL subtypes and functions will also be studied. Furthermore, the effects of AhR activation on the expression of IL-7 and KGF in the crosstalk between IEL and IEC will be investigated. Moreover, we will investigate the role of cytokines derived from IEL in the regulation of intestinal barrier function. This proposal would give insight into the mechanism of AhR in maintaining intestinal barrier homeostasis and may provide novel strategy to prevent the loss of intestinal barrier function.