IL-22+ -γδT17细胞通过WNT3a信号通路改善肠道GVHD的机制研究

肠道急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植(allo-HSCT)后严重并发症，死亡率高。我们在前期研究中首次发现allo-HSCT后γδT17细胞是肠道aGVHD中发挥保护作用的关键细胞亚群，并通过分泌IL-22促进肠道干细胞修复并维护肠道稳态，IL-22还能有效促进Wnt信号通路相关基因的表达，提示WNT途径可能是IL-22下游调节肠道动态平衡的关键因素。因此我们提出假说：γδT17细胞作为肠道aGVHD中发挥保护作用的关键细胞亚群，通过分泌IL-22靶向肠道干细胞（ISC），WNT信号通路是其促进ISC增殖，恢复肠道稳态，减轻肠道aGVHD的可能机制。本项目拟在前期的基础上通过单细胞RNAseq、质谱流式、活体示踪等技术对γδT17细胞分泌IL-22通过WNT3a信号改善肠道GVHD的机制深入研究，为寻找aGVHD的有效防治新策略提供理论依据。

Intestinal acute graft-versus-host disease (aGVHD) is the most severe complication with a high mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In previous studies ,we firstly discovered that γδT17 cell is the key cellular group contributing to the protective property in intestinal aGVHD after allo-HSCT. γδT17 cell secrete IL-22 to promote intestinal stem cell repair and maintain intestinal homeostasis. IL-22 promote the expression of genes related to Wnt signaling pathway, suggesting that the WNT pathway may be a key factor in regulating the dynamic balance of intestinal tract downstream of IL-22. Therefore, we propose a hypothesize that γδT17 cell is a key cell group that plays a protective role in the intestinal aGVHD. By secreting IL-22 to target intestinal stem cells, the WNT signaling pathway is probable mechanism to reduces intestinal aGVHD via promotes ISC proliferation, restores intestinal homeostasis. This project intends to further investigate on the mechanism of γδT17 cells regulating IL22 to protect GVHD in the intestinal tract through WNT3a signals through single cell RNAseq, mass spectrometry flow cytometry and in vivo tracing on the basis of previous studies. This project is supposed to contribute to discovering possible machanism and effective prevevtion in aGVHD and provide a theoretical basis for developing new therapies.