持续性炎症-免疫抑制-分解代谢综合征（PICS）是导致脓毒症患者后期死亡的重要原因，其具体机制不明。CD4+T淋巴细胞减少是脓毒症PICS发生的关键。申请者利用RNA-seq分析发现PICS患者CD4+T淋巴细胞DDX3X mRNA表达升高，且与PICS的进展和预后不良相关。进一步研究发现，DDX3X mRNA表达上调与CD4+T淋巴细胞数量减少有关，同时伴随NLRP3/caspase-1表达上调。据此推测：在脓毒症中，DDX3X表达上调激活NLRP3/caspase-1信号通路，介导CD4+T淋巴细胞焦亡，促进脓毒症PICS的发生发展。本项目拟在条件性敲除小鼠和细胞模型中，系统研究DDX3X对CD4+T淋巴细胞焦亡的影响，及其在脓毒症PICS发生中的作用，并进一步阐明其分子机制。本研究将为认识脓毒症PICS的发生机制提供新视角，并探索新的治疗靶点。

Persistent inflammation-immunosuppression-catabolic syndrome (PICS) is the important reason of late death in sepsis patients, and its mechanism is still unknown. The decrease of CD4+ T lymphocytes is known to be the key factor of sepsis induced PICS. RNA-sequence analysis indicated that DDX3X mRNA up-regulated in CD4+T lymphocytes of PICS patients and correlated with the progression and poor prognosis of PICS. Furthermore, the up-regulation of DDX3X mRNA expression is not only related to the loss of CD4+ T cells, but also accompanied by the up-regulation of NLRP3/caspase-1 expression. Therefore, we hypothesize that DDX3X may regulate the pyroptosis and immunosuppression of CD4+T lymphocyte through activating NLRP3/caspase-1 signaling pathway, therefore accelerate the sepsis induced PICS. In the current project, we will elucidate the role of DDX3X in CD4+ T lymphocytes pyroptosis and its mechanism in the process of sepsis induced PICS in conditional knockout mice and cellular model. The study will provide a new horizon to understand the mechanism of PICS and novel strategies for the treatment.