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From thymus to periphery: Molecular basis of effector γδ‐T cell differentiation
Immunological Reviews ( IF 8.7 ) Pub Date : 2020-11-15 , DOI: 10.1111/imr.12918
Gina J Fiala 1 , Anita Q Gomes 1, 2 , Bruno Silva-Santos 1
Affiliation  

The contributions of γδ T cells to immune (patho)physiology in many pre‐clinical mouse models have been associated with their rapid and abundant provision of two critical cytokines, interferon‐γ (IFN‐γ) and interleukin‐17A (IL‐17). These are typically produced by distinct effector γδ T cell subsets that can be segregated on the basis of surface expression levels of receptors such as CD27, CD44 or CD45RB, among others. Unlike conventional T cells that egress the thymus as naïve lymphocytes awaiting further differentiation upon activation, a large fraction of murine γδ T cells commits to either IFN‐γ or IL‐17 expression during thymic development. However, extrathymic signals can both regulate pre‐programmed γδ T cells; and induce peripheral differentiation of naïve γδ T cells into effectors. Here we review the key cellular events of “developmental pre‐programming” in the mouse thymus; and the molecular basis for effector function maintenance vs plasticity in the periphery. We highlight some of our contributions towards elucidating the role of T cell receptor, co‐receptors (like CD27 and CD28) and cytokine signals (such as IL‐1β and IL‐23) in these processes, and the various levels of gene regulation involved, from the chromatin landscape to microRNA‐based post‐transcriptional control of γδ T cell functional plasticity.

中文翻译:

从胸腺到外周:效应子 γδ-T 细胞分化的分子基础

在许多临床前小鼠模型中,γδ T 细胞对免疫(病理)生理学的贡献与其快速和大量提供两种关键细胞因子有关,干扰素-γ(IFN-γ)和白细胞介素-17A(IL-17) . 这些通常由不同的效应子 γδ T 细胞亚群产生,这些亚群可以根据受体(如 CD27、CD44 或 CD45RB 等)的表面表达水平进行分离。不同于传统的 T 细胞作为幼稚淋巴细胞离开胸腺,等待激活后进一步分化,大部分鼠 γδ T 细胞在胸腺发育过程中表达 IFN-γ 或 IL-17。然而,胸外信号既可以调节预编程的 γδ T 细胞;并诱导幼稚 γδ T 细胞外周分化为效应细胞。在这里,我们回顾了小鼠胸腺中“发育预编程”的关键细胞事件;以及效应器功能维持与外围可塑性的分子基础。我们强调了我们对阐明 T 细胞受体、辅助受体(如 CD27 和 CD28)和细胞因子信号(如 IL-1β 和 IL-23)在这些过程中的作用以及所涉及的不同水平的基因调控的一些贡献,从染色质景观到基于 microRNA 的 γδ T 细胞功能可塑性的转录后控制。
更新日期:2020-11-27
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