异常2型免疫反应是脓毒症预后不良的重要原因。Ⅱ型固有淋巴细胞（ILC2）的增殖活化在始动异常2型免疫反应中发挥重要作用。研究报道晚期糖基化终末产物受体（RAGE）及其介导的信号通路，通过调节ILC2活性，触发并介导异常2型免疫反应。我们前期研究发现脓毒症小鼠肺组织中ILC2大量募集，且与肺泡灌洗液中IL-5、IL-13等2型炎症因子水平相关；RAGE基因敲除小鼠脓毒症模型肺泡灌洗液中2型炎症因子水平显著降低，且肺组织中ILC2线粒体数量明显减少，提示线粒体生物发生受抑制。因此推测：RAGE可能通过调控ILC2线粒体生物发生，在脓毒症异常2型免疫反应和肺损伤中发挥重要作用。本项目通过动物实验和临床研究相结合，从整体、细胞、细胞器和分子水平多个层面系统阐明上述假说，为探索脓毒症免疫调节治疗新策略提供理论依据。

Abnormal type 2 immune response is considered as a major cause of sepsis-induced lethality. The proliferation and activation of type 2 innate lymphoid cell (ILC2) is essential in initiating abnormal type 2 immune response. Moreover, RAGE and mediated signaling pathway is reported to be involved in type 2 immune response via modulating ILC2 activity. Our previous studies demonstrated that in septic mice lung tissue, ILC2 was largely infiltrated which was associated with type 2 cytokine levels (IL-5, IL-13, et al) expressed in bronchoalveolar lavage fluid. Furthermore, we found that in RAGE knockout septic mice, the number and mitochondrial mass of lung ILC2 were significant decreased that was accompanied with reduced type 2 cytokines in bronchoalveolar lavage fluid. Therefore, taken together with previous research and our existing results, we hypothesize that RAGE may exert an important effect in abnormal type 2 immune response and lung injury via mediating ILC2 mitochondrial biogenesis in sepsis. The present project aims to comprehensively evaluate the underlying mechanism behind RAGE mediated sepsis using in vivo, in vitro and ex vivo model. This project will help to shed new light on the immune intervention of sepsis.