IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation.
IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation.
复制标题
DOI：
10.1016/j.intimp.2016.08.012
复制
发表时间：
2016-10
影响因子：
5.6
通讯作者：
K. Zhao;Suhong Ruan;Yu Tian;Dong-mei Zhao;Chong Chen;B. Pan;Zhi-ling Yan;Lingling Yin;
中科院分区：
文献类型：
--
作者：
K. Zhao;Suhong Ruan;Yu Tian;Dong-mei Zhao;Chong Chen;B. Pan;Zhi-ling Yan;Lingling Yin;
移植物抗宿主病（GVHD）是骨髓干细胞移植后的一种严重并发症，与同种异体反应性供者T细胞分泌的大量促炎细胞因子有关。本课题组及其他研究发现，白细胞介素-22（IL-22）可加重GVHD的靶器官损害。然而，IL-22在小鼠急性GVHD中的作用机制和信号通路尚不清楚。在此，我们观察到与GVHD组相比，注射IL-22的小鼠中检测到更严重的病理损伤和更多的CD 3 +T细胞浸润在GVHD靶器官中。与Th 1、Th 17和Th 22细胞相关的转录因子T-bet、RORγt和AhR在不同GVHD靶器官中也有不同程度的变化。IL-22处理组GVHD小鼠IL-22 R及其下游蛋白P-STAT 3表达增加。这些结果表明，IL-22在GVHD靶器官中的病理作用有助于外源性注射IL-22以及从浸润的同种异体反应性效应T细胞分泌IL-22。此外，IL-22 R-STAT 3通路可能在GVHD组织损伤中起重要作用，靶向该途径可能产生减少GVHD的新方法。
Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3+T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORγt and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD.