Chen Longwang, Ke Heliang, Zhang Yaolu, Jin Pinpin, Liu Xinyong, Hong Guangliang, Zhao Guangju, Lu Zhongqiu, Wu Bin
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China.
Heliyon. 2022 Dec 6;8(12):e12082. doi: 10.1016/j.heliyon.2022.e12082. eCollection 2022 Dec.
Immune paralysis induced by sepsis, especially dysfunction of CD4 T cells, leads to an increased risk of infection. In sepsis, abnormal differentiation of T lymphocytes is associated with multiorgan dysfunction syndrome. In T lymphocytes, the Orai1/nuclear factor of activated T Cells (NFAT) pathway is a critical mediator of infection, inflammation, and autoimmunity. In this study, we confirmed immunosuppression of splenic CD4 T cells and abnormal differentiation of T lymphocytes in septic mice. Furthermore, we found that the Orai1/NFAT signaling pathway was inhibited in septic mice; however, the overexpression of Orai1 not only improved immune function of T cells in sepsis but also reduced the mortality and organ damage in septic mice. Moreover, the overexpression of Orai1 could reverse the increases in the numbers of T regulatory and T helper 17 cells in septic mice. These data suggest that the Orai1-mediated NFAT signaling pathway can improve sepsis-induced T-lymphocyte immunosuppression and acute organ dysfunction.
脓毒症诱导的免疫麻痹，尤其是CD4 T细胞功能障碍，会导致感染风险增加。在脓毒症中，T淋巴细胞的异常分化与多器官功能障碍综合征相关。在T淋巴细胞中，Orai1/活化T细胞核因子（NFAT）途径是感染、炎症和自身免疫的关键介质。在本研究中，我们证实了脓毒症小鼠脾脏CD4 T细胞的免疫抑制和T淋巴细胞的异常分化。此外，我们发现脓毒症小鼠中Orai1/NFAT信号通路受到抑制；然而，Orai1的过表达不仅改善了脓毒症中T细胞的免疫功能，还降低了脓毒症小鼠的死亡率和器官损伤。此外，Orai1的过表达可以逆转脓毒症小鼠中调节性T细胞和辅助性T细胞17数量的增加。这些数据表明，Orai1介导的NFAT信号通路可以改善脓毒症诱导的T淋巴细胞免疫抑制和急性器官功能障碍。
