Recent advances in understanding the Th1/Th2 effector choice.
Recent advances in understanding the Th1/Th2 effector choice.
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DOI：
10.12703/r/10-30
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Butcher MJ;Zhu J
自Mosmann和Coffman在1986年提出开创性的“1型T辅助细胞（Th 1）/2型T辅助细胞（Th 2）”假说以来的35年中，免疫学界已经认识到幼稚的CD 4 T细胞需要在其活化时做出重要决定，即向Th 1、Th 2、Th 17分化。（产生白细胞介素-17的T辅助细胞）、滤泡性T辅助细胞（Tfh）或调节性T细胞（Treg）的命运来协调各种适应性免疫应答。Th 1/Th 2效应器命运选择的主要分子基础最初已使用出色的还原论体外培养系统进行了表征，通过该系统，转录因子T-bet和GATA 3被确定为Th 1和Th 2细胞分化的主要调节因子。然而，Th 1/Th 2细胞分化及其细胞异质性通常由多种转录因子的组合表达决定，特别是在体内，其中树突状细胞（DC）和先天性淋巴样细胞（ILC）亚群也可以影响T辅助细胞谱系的选择。此外，还发现能够诱导Th 17细胞分化的炎性细胞因子在典型的Th 1-或Th 2-相关免疫应答期间被诱导，导致从Th 17细胞表型向Th 1或Th 2细胞转变的替代分化途径。在这篇综述中，我们将讨论该领域的最新进展，重点是一些新的球员在转录网络，贡献的DC和ILC，和替代分化途径，了解Th 1/Th 2效应器的选择在体内。
For over 35 years since Mosmann and Coffman proposed the seminal “type 1 T helper (Th1)/type 2 T helper (Th2)” hypothesis in 1986, the immunological community has appreciated that naïve CD4 T cells need to make important decisions upon their activation, namely to differentiate towards a Th1, Th2, Th17 (interleukin-17-producing T helper), follicular T helper (Tfh), or regulatory T cell (Treg) fate to orchestrate a variety of adaptive immune responses. The major molecular underpinnings of the Th1/Th2 effector fate choice had been initially characterized using excellent reductionist in vitro culture systems, through which the transcription factors T-bet and GATA3 were identified as the master regulators for the differentiation of Th1 and Th2 cells, respectively. However, Th1/Th2 cell differentiation and their cellular heterogeneity are usually determined by a combinatorial expression of multiple transcription factors, particularly in vivo, where dendritic cell (DC) and innate lymphoid cell (ILC) subsets can also influence T helper lineage choices. In addition, inflammatory cytokines that are capable of inducing Th17 cell differentiation are also found to be induced during typical Th1- or Th2-related immune responses, resulting in an alternative differentiation pathway, transiting from a Th17 cell phenotype towards Th1 or Th2 cells. In this review, we will discuss the recent advances in the field, focusing on some new players in the transcriptional network, contributions of DCs and ILCs, and alternative differentiation pathways towards understanding the Th1/Th2 effector choice in vivo.