骨髓抑制细胞是一群具有免疫抑制功能的未成熟骨髓细胞分化成熟受阻而形成的异质细胞。近年的研究发现骨髓抑制细胞在脓毒症小鼠的骨髓、脾脏和肝脏明显增多，在脓毒症的高炎症反应阶段发挥了重要的免疫调节作用。本课题组多年的研究证实热休克因子1抑制LPS所致的炎症反应和中性粒细胞浸润从而保护多系统器官损伤。但是热休克因子1是否调控脓毒症骨髓抑制细胞的动员和活化从而保护脓毒症的多系统器官损伤，国内外尚未见报道。本项目拟采用HSF1-/-小鼠探讨HSF1缺失对脓毒症骨髓抑制细胞的动员和活化的影响及对脓毒症晚期细菌清除能力、免疫效应细胞的凋亡、T细胞增殖以及Th2极化的影响，并从转录水平研究HSF1对与骨髓抑制细胞扩增和活化相关因子的调控，对于揭示HSF1在脓毒症的作用具有十分重要的学术意义。

Myeloid-derived suppressor cells (MDSCs)are a heterogeous population of cells which result from the block in the differentiation of immature myeloid cells into mature myeloid cells during pathological conditions. Recent studies demonstrated that MDSCs numbers dramatically increase in the bone marrow, spleen and liver and play a critical role during hyperinflammatory phase of sepsis in mice. Our previous data confirm that HSF1 is essential in protection against the lethal systemic inflammation and the neutriphil infiltration induced by LPS. The role of HSF1 in the expansion and activation of MDSCs during sepsis is unknown. In the present study, sepsis will be induced by caecal ligation and puncture in HSF1-/- or HSF1+/+ mice. The expansion of MDSCc will be investigated and the expression of expansion relative factors will be detected. To address whether HSF1 regulate the activation and function of MSDCS, the bacterial clearance, apoptosis of immune effector cells, proliferation of T cells and Th2 polarization will be analyzed during late sepsis phase. Furthermore, EMSA and reporter plasmids will be used to identify the targets regulated by HSF1. Our project will provide new evidences for the role HSF1 in sepsis.