肠道急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植后最富挑战性的并发症之一，髓系来源的抑制性细胞（MDSC）为抗肠道aGVHD的关键免疫细胞。我们团队建立了IL-22高效诱导体系并发现其为肠道保护因子，但aGVHD发生时IL-22来源受损。我们前期证明MDSC可通过Arg-1对肠道aGVHD发挥保护作用，且回输MDSC后可引起小鼠肠道IL-22及AhR同步性表达上调，提示aGVHD发生时肠道MDSC可能通过Arg-1调控T细胞中IL-22表达，且AhR参与该信号通路。本项目拟采用体外细胞共培养、特异性蛋白抑制剂、特异性通路阻断剂、单细胞检测等手段从细胞和分子水平研究MDSC通过AhR/ARNT信号通路促进T细胞IL-22表达能力的作用及分子机制，并在小鼠aGVHD模型中验证上述分子机制。本研究将为揭示MDSC调控aGVHD新机制、阐明肠道免疫细胞及因子相互作用网络提供理论依据。

Intestinal acute graft-versus-host disease (aGVHD) is one of the most challenging complications after allogeneic hematopoietic stem cell transplantation, and myeloid-derived suppressor cells (MDSC) are key immune cells against aGVHD in the intestine. Our team established an efficient induction system for IL-22 and found it to be an intestinal protective factor, but the source of IL-22 was damaged when aGVHD occurred. We have previously demonstrated that MDSC can play a protective role against intestinal aGVHD through Arg-1, and the infusion of MDSC can cause synchronous expression of IL-22 and AhR in the intestine, suggesting that when aGVHD occurs intestinal MDSC may regulates IL-22 expression in T cells through Arg-1, and AhR is involved in this signaling pathway. This project intends to use in vitro cell co-culture, specific protein inhibitors, specific pathway blockers, single cell technologies to study the role of MDSC in promoting the expression of IL-22 in T cells through the AhR / ARNT signaling pathway from the cellular and molecular levels, and verify the above molecular mechanism in the mouse aGVHD model. This study will provide a theoretical basis for revealing the new mechanism of MDSC in aGVHD and elucidating the crosstalk network of intestinal immune cells and cytokines.