Exosomes derived from plasma of septic patients inhibit apoptosis of T lymphocytes by down-regulating bad via hsa-miR-7-5p

Abstract

Immunosuppression is currently a vital pathophysiological characteristic and core problem of sepsis. Apoptosis of T lymphocyte contribute to immunosuppression by decreasing immune effector cells. A report has recently revealed the potential regulatory role of exosomal miRNAs derived from plasma of septic patients on immune system, but the underlying mechanism is unclear. We discovered the antiapoptotic effect of circulating exosomes derived from plasma of septic patients (Sepsis-Exos) on T lymphocytes and further investigated the molecular mechanism. Next-generation sequencing (NGS) indicated that sepsis induces prominent change of exosomal miRNA expression profile, including the overexpressed hsa-miR-7-5p. Gene Bad, which is in the cGMP-PKG signaling pathway, was negatively regulated by hsa-miR-7-5p by dual luciferase reporter assay. Sepsis-Exos were demonstrated to downregulate the mRNA and protein levels of proapoptotic gene Bad, active Caspase-3 and Bax, while upregulate that of antiapoptotic gene Bcl-2 via hsa-miR-7-5p, thus inhibited apoptosis of T lymphocytes induced by lipopolysaccharide (LPS) in vitro. Furthermore, Sepsis-Exos was verified to inhibit T lymphocytes apoptosis during sepsis in vivo, reducing mortality rate of septic model mice. In conclusion, we provide evidence that Sepsis-Exos participate in ameliorating apoptosis of T lymphocytes by directly suppressing Bad via hsa-miR-7-5p.