Orai1 Mediated Calcium Influx Improves Sepsis-induced T Lymphocyte Immunosuppression and Acute Organ Dysfunction

Abstract Sepsis-triggered immune paralysis, particularly CD4 + T-cell dysfunction, increases susceptibility to infections. Ca 2+ signals arising from store-operated calcium entry (SOCE) in T lymphocytes are critical mediators to infection, inflammation, and autoimmunity. Orai1 is a major component of SOCE. The role of Orai1 and SOCE in sepsis-induced immunosuppression remain to be elucidated. In this study, we first identified the immunosuppression of splenic CD4 + T cells and CD4 + CD25 + Treg cell/T helper 17 (Th17) cell imbalance in septic mice. Following this, we found that Ca 2+ -calcineurin-calcineurin-nuclear factor of activated T cell (NFAT) signaling pathways as well as SOCE were inhibited in septic mice. Further, Upregulation of Orai1 not only can improve immune function of T cell in sepsis but also reduce the mortality and organ damage in septic mice. Lastly, Overexpression of Orai1 can partially recovery of SOCE in sepsis. These data suggest that Orai1 mediated calcium influx can improve sepsis-induced T lymphocyte immunosuppression and acute organ dysfunction.