Hirahara Kiyoshi, Nakayama Toshinori
Department of Advanced Allergology of the Airway, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan.
Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan AMED-CREST, The Japan Agency for Medical Research and Development (AMED), 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan
Int Immunol. 2016 Apr;28(4):163-71. doi: 10.1093/intimm/dxw006. Epub 2016 Feb 12.
CD4(+)T cells are crucial for directing appropriate immune responses during host defense and for the pathogenesis of inflammatory diseases. In addition to the classical biphasic model of differentiation of T-helper 1 (Th1) and Th2 cells, unexpected increases in the numbers of CD4(+)T-cell subsets, including Th17, Th9, T follicular-helper (Tfh) and T-regulatory (Treg) cells, have been recognized. In the present review, we focus on how these various T-helper cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. In particular, we focus on multiple sclerosis, psoriasis and asthma as typical model diseases in which multiple T-helper cell subsets have recently been suggested to play a role. We will also discuss various unique sub-populations of T-helper cells that have been identified. First, we will introduce the heterogeneous T-helper cell subsets, which are classified by their simultaneous expression of multiple key transcription factors. We will also introduce different kinds of memory-type Th2 cells, which are involved in the pathogenesis of chronic type-2 immune-related diseases. Finally, we will discuss the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T-helper cell subsets. The latest progress in the study of T-helper cell subsets has forced us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the Th1/Th2 balance. To this end, we propose another model--the pathogenic T-helper population disease-induction model--as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases.
CD4(+)T细胞在宿主防御过程中引导适当的免疫反应以及在炎症性疾病的发病机制中起着关键作用。除了经典的辅助性T细胞1（Th1）和Th2细胞双相分化模型外，人们还认识到包括Th17、Th9、滤泡辅助性T（Tfh）和调节性T（Treg）细胞在内的CD4(+)T细胞亚群数量意外增加。在本综述中，我们重点关注这些不同的辅助性T细胞亚群如何促成免疫介导的炎症性疾病的发病机制。特别是，我们将多发性硬化症、银屑病和哮喘作为典型的模型疾病进行重点讨论，最近有人提出多种辅助性T细胞亚群在这些疾病中发挥作用。我们还将讨论已确定的辅助性T细胞的各种独特亚群。首先，我们将介绍异质性辅助性T细胞亚群，它们通过多种关键转录因子的同时表达进行分类。我们还将介绍不同类型的记忆性Th2细胞，它们参与慢性2型免疫相关疾病的发病机制。最后，我们将讨论辅助性T细胞亚群可塑性和异质性产生的分子机制。辅助性T细胞亚群研究的最新进展迫使我们重新思考基于Th1/Th2平衡模型之外的免疫介导炎症性疾病的病因。为此，我们提出另一种模型——致病性辅助性T细胞群体疾病诱导模型——作为免疫介导炎症性疾病诱导和/或持续存在的一种可能机制。
