Orai1 overexpression improves sepsis-induced T-lymphocyte immunosuppression and acute organ dysfunction in mice
Longwang Chen,
Heliang Ke,
Yaolu Zhang,
Pinpin Jin,
Xinyong Liu,
Guangliang Hong,
Guangju Zhao,
Zhongqiu Lu,
Bin Wu
Affiliations
Longwang Chen
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China
Heliang Ke
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China
Yaolu Zhang
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China
Pinpin Jin
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China
Xinyong Liu
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China
Guangliang Hong
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China
Guangju Zhao
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China; Corresponding author.
Zhongqiu Lu
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China; Corresponding author.
Bin Wu
Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China; Corresponding author.
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.
