摘要
脓毒症免疫失衡中Th17细胞发挥重要作用，作为具有高度可塑性的细胞群体，Th17细胞已经被证明内部存在表达多种特征性转录因子的亚群（如表达T-bet的Th1样Th17细胞等），可能在不同诱导条件下产生不同的转分化结局。转录因子T-bet作为Th1细胞分化的驱动者，近年来被证明可以通过阻断Rorc基因的反式激活，抑制Th17细胞分化。因此，T-bet的表达水平在一定程度上可以决定Th17细胞的转分化方向，尤其是在多种感染性疾病模型中，T-bet敲除促进Th17细胞分化，增强了免疫应答水平，且敲除T-bet能有效降低小鼠流感病毒-细菌二次感染模型的病死率。但另一方面，小鼠Th17细胞中特异性敲除T-bet影响Th17至Th1转分化，导致脓毒症小鼠肾脏细菌载量增加。上述看似对立的现象提示，T-bet作为Th1、Th17细胞分化中的“桥梁性”分子，在免疫调节中究竟是增强“保护性免疫反应”还是加剧“病理性免疫反应”或许与更复杂的生理机制相关。本文通过介绍转录因子T-bet在Th17细胞分化中的作用，对T-bet这一关键分子在机体免疫应答中的特殊功能进行讨论，为脓毒症等感染性疾病提供新的免疫学思考视角。
Abstract
With high plasticity, Th17 cells play a key role in immune imbalance in sepsis, which have been shown to harbor subgroups expressing a variety of characteristic transcription factors, such as Th1-like Th17 cells specifically expressing T-bet, may producing diverse transdifferentiation outcomes under different induction conditions. The transcription factor T-bet, as driver of Th1 cell differentiation, has been shown in recent years to inhibit Th17 cells differentiation by repressing the transactivation of Rorc. Thus, T-bet expression may influence transdifferentiation of Th17 cells, especially in infectious disease models, where T-bet knockout promotes Th17 cell differentiation and enhances immune response, loss of T-bet confers survival advantage to influenza-bacterial superinfection; besides, specific knockout of T-bet in mice Th17 cells impair Th17-to-Th1 transdifferentiation, resulting in increased bacterial load in the kidneys of CLP mice. This seemingly contradictory phenomenon suggests that T-bet, as a "Bridge" molecule in Th1 and Th17 cells differentiation, may enhance protective immune response or aggravate pathological immune responses under different situations. The function of transcription factor T-bet in Th17 cell differentiation is introduced, and the special role of T-bet in immune response is discussed, this review may provide a brand new immunological perspective for sepsis and other infectious diseases.
基金项目
国家自然科学基金重点项目(81930058)
江苏省重症医学重点实验室项目(BM2020004)
江苏省重点研发计划(社会发展)重点项目(BE2019749)
万方数据