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中华重症医学电子杂志 ›› 2023, Vol. 09 ›› Issue (03) : 280 -285. doi: 10.3877/cma.j.issn.2096-1537.2023.03.008

综述

T-bet:脓毒症免疫失衡中Th17细胞的新型调节分子
高超, 巢杰, 邱海波()   
  1. 210009 南京,江苏省重症医学重点实验室 东南大学附属中大医院重症医学科
    210009 南京,东南大学医学院生理学系
  • 收稿日期:2022-08-12 出版日期:2023-08-28
  • 通信作者: 邱海波
  • 基金资助:
    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--临床前沿技术(BE2019749)

Emerging roles of transcription factor T-bet of Th17 in immune imbalance of sepsis

Chao Gao, Jie Chao, Haibo Qiu()   

  1. Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
    Department of Physiology, School of Medicine, Southeast University, Nanjing 210009, China
  • Received:2022-08-12 Published:2023-08-28
  • Corresponding author: Haibo Qiu
引用本文:

高超, 巢杰, 邱海波. T-bet:脓毒症免疫失衡中Th17细胞的新型调节分子[J]. 中华重症医学电子杂志, 2023, 09(03): 280-285.

Chao Gao, Jie Chao, Haibo Qiu. Emerging roles of transcription factor T-bet of Th17 in immune imbalance of sepsis[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(03): 280-285.

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。

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.

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