间充质干细胞外泌体治疗炎症性肠病的新途径：通过TSG-6调控CD4+T细胞功能？

炎症性肠病（IBD）的发病机制尚不明确，以CD4+T细胞为主的适应性免疫失衡是其发生并呈持续状态的中心环节。间充质干细胞（MSCs）可通过抑制T细胞免疫反应改善肠道炎症，但其归巢能力有限。而MSCs分泌的外泌体（MSCs-Exo）具有其大部分功能，无恶性分化且性质稳定，可弥补MSCs移植的不足。MSCs分泌的肿瘤坏死因子α刺激基因6（TSG-6）可抑制T细胞活化、促进Treg细胞产生，减轻肠道炎症。MSCs-Exo是否通过呈递TSG-6调控CD4+T分化功能尚未阐明。本课题拟应用MSCs-Exo干预急、慢性实验性结肠炎小鼠，并分离小鼠naïve CD4+T细胞与MSCs-Exo共培养，从体内外两方面探讨MSCs-Exo对CD4+T细胞分化功能的影响；对比敲低TSG-6前后MSCs-Exo对实验性结肠炎的治疗作用和CD4+T细胞的变化，探讨TSG-6的调控作用，为临床治疗IBD提供新思路。

The pathogenesis of inflammatory bowel disease (IBD) is still unclear, and the adaptive immune imbalance dominated by CD4+T cells is the main link of its occurrence and persistence. Mesenchymal stem cells (MSCs) could alleviate intestinal inflammation by suppressing the immune response of T cells, which is expected to become a new treatment for IBD. However, their homing ability is limited. Exosomes secreted by MSCs (MSCs-Exo) have the most of functions of MSCs, have no malignant differentiation and are stable, which can make up for the deficiency of MSCs therapy. The role of inhibition T cells activation, promoting the production of Treg cells and reducing intestinal inflammation of tumor necrosis factor-α-stimulated gene 6 (TSG-6) secreted by MSCs had been found. Consequently, our hypothesis is that MSCs-Exo may regulate CD4+T differentiation by TSG-6. In this study, MSCs-Exo was used to acute and chronic experimental colitis in mice and co-cultured with naïve CD4+T to investigate the effect of MSCs-Exo on the proliferation, activation and differentiation of CD4+T cells in vivo and in vitro. In addition, this work will compare the therapeutic effect of MSCs-Exo on experimental colitis and the changes of CD4+T cells after TSG-6 reduction. This study preliminarily elucidated the immune regulatory mechanism of MSCs-Exo in IBD, providing a new theoretical and experimental basis for the clinical treatment of IBD.