miR-155调控髓源性抑制细胞对脓毒症晚期小鼠免疫抑制的实验研究

免疫抑制是脓毒症晚期继发院内感染及高病死率的重要原因，研究发现髓源抑制细胞（MDSCs）异常表达和活化与脓毒症免疫抑制密切相关。miR-155 在免疫反应的调节中起重要作用，本课题组既往研究证实miR-155可以调控巨噬细胞介导的免疫反应，减轻脓毒症急性肺损伤。我们预实验发现脓毒症晚期小鼠模型中MDSCs比例显著增加，并伴miR-155表达上调。 miR-155可能参与了MDSCs介导的脓毒症晚期免疫抑制反应。为验证这一假说，本申请项目拟通过构建小鼠脓毒症晚期动物模型，提取MDSCs，采用RNA干扰、基因过表达和T细胞共培养等手段，系统研究miR-155对MDSCs增殖、活化的影响，阐明其分子调控机制；进一步通过体内转染miR-155，深入探讨其在MDSCs介导的脓毒症晚期免疫抑制中的作用。该研究对脓毒症晚期免疫抑制的发病机制及探索脓毒症新的治疗方法具有重要意义。

Immunosuppression is an important cause of secondary nosocomial infection and high mortality in late sepsis, studies have found that the abnormal expression and activation of myeloid derived suppressor cells (MDSCs) are closely related to the immunosuppression of sepsis. miR-155 plays an important role in the regulation of immune response, our research group have confirmed that miR-155 can regulate the immune response mediated by macrophages and reduce acute lung injury in sepsis.Our preliminary experiment have found that the proportion of MDSCs in the late model of sepsis is significantly increased and the expression of miR-155 is up-regulated. miR-155 may be involved in late sepsis immunosuppression mediated by MDSCs. To test this hypothesis, this project aims to study the effect of miR-155 on the proliferation and activation of MDSCs and elucidate its molecular regulation mechanism by means of RNA interference, gene overexpression and T cell co-culture, and explore the role of miR-155 on MDSCs-mediated late sepsis immunosuppression through miR-155 transfection in vivo.This study is of great significance for studying the pathogenesis of late sepsis immunosuppression and the exploration of new treatment of sepsis.