共生真菌对肠黏膜固有层巨噬细胞极化的调节及其在小肠移植免疫排斥中的机制

Macrophages in mucosal lamina propria play an important role in maintaining gut immune balance. The destruction of gut symbiotic microorganisms after the intestine transplantation (IT) may lead to severe immune rejection. Fungi are increasingly being found to be an important component of gut microbes. We have already found that fungal composition in Intestinal mucosal is imbalanced after IT; The mouse of CARD9 selective knockout were found a more severe gut inflammation after IT; symbiotic fungi promote macrophage cell to differentiate into M1 type, and inhibit its differentiation into M2 type. Therefore, we speculate that after the IT, the fungi stimulate NF-kB by activating its receptor and CARD9 pathway, while inhibit ERK, to promote macrophage polarization to M1 instead of M2. It plays an important role in maintaining the immune balance of IT. We will study the effects of fungi on the polarization of macrophages in the lamina propria of the gut after IT, from molecular, cellular, organ levels, trying to find the molecular mechanism. We want to find the function of symbiotic fungi in maintaining immune balance after IT, also to provide new ideas for treatment.

肠黏膜固有层巨噬细胞在维持肠道免疫平衡中发挥重要作用。小肠移植术后肠道共生微生物的平衡破坏将导致移植后免疫反应的发展。真菌越来越被发现是肠道微生物的重要组成部分。我们的预实验发现小鼠小肠移植急排期移植肠粘膜真菌组成失衡；选择性敲除小鼠CARD9，小肠移植后移植肠肠道炎症明显增加；前期获得的共生真菌促进巨噬细胞株和小鼠腹腔巨噬细胞向M1型分化，而抑制其向M2型分化。由此我们推测，小肠移植术后急排期，共生真菌通过激活其受体和CARD9途径刺激NF-kB，抑制ERK，促进肠黏膜固有层巨噬细胞向M1型方向极化，抑制其向M2型方向极化，在小肠移植免疫平衡维持方面发挥重要作用。本课题将从分子、细胞、器官和整体层面研究小肠移植后共生真菌对肠道固有层巨噬细胞极化的影响，其分子机制及生理意义，揭示共生真菌在维持免疫平衡方面的功能，为小肠移植的治疗提供新的思路。

肠黏膜固有层巨噬细胞在维持肠道免疫平衡中发挥重要作用。小肠移植术后肠道共生微生物的平衡破坏将导致移植后免疫反应的发展。真菌越来越被发现是肠道微生物的重要组成部分。我们的预实验发现小肠移植急排期移植肠粘膜真菌组成失衡；选择性敲除小鼠CARD9，小肠移植后移植肠肠道炎症明显增加；共生真菌促进巨噬细胞株和小鼠腹腔巨噬细胞向M1型分化，而抑制其向M2型分化。由此我们推测，小肠移植术后急排期，真菌通过激活其受体和CARD9途径刺激NF-kB，抑制ERK，促进巨噬细胞向M1型方向极化，抑制其向M2型方向极化，在小肠移植免疫平衡维持方面发挥重要作用。本课题从分子、细胞、器官和整体层面研究小肠移植后真菌对肠道固有层巨噬细胞极化的影响，其分子机制及生理意义，揭示共生真菌在维持免疫平衡方面的功能，为小肠移植的治疗提供新的思路。