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

doi:10.1016/j.heliyon.2022.e12082

Orai1 overexpression improves sepsis-induced T-lymphocyte immunosuppression and acute organ dysfunction in mice

Heliyon. 2022 Dec 6;8(12):e12082. doi: 10.1016/j.heliyon.2022.e12082. eCollection 2022 Dec.

Authors

Longwang Chen^{1

2}, Heliang Ke^{1

2}, Yaolu Zhang^{1

2}, Pinpin Jin^{1

2}, Xinyong Liu^{1

2}, Guangliang Hong^{1

2}, Guangju Zhao^{1

2}, Zhongqiu Lu^{1

2}, Bin Wu^{1

2}

Affiliations

¹ Emergency Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
² Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou 325000, China.

Abstract

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.

Keywords: Immunosuppression; NFAT; Orai1; Sepsis; Th17; Treg.