CD3bright signals on γδ T cells identify IL-17A-producing Vγ6Vδ1+ T cells
CD3bright signals on γδ T cells identify IL-17A-producing Vγ6Vδ1+ T cells
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DOI：
10.1038/icb.2014.94
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发表时间：
2015-02-01
影响因子：
4
通讯作者：
Smyth, M. J.
中科院分区：
文献类型：
--
作者：
Paget, C.;Chow, M. T.;Smyth, M. J.
白细胞介素-17A (IL-17A) 是一种促炎细胞因子，在感染、过敏和自身免疫等多种免疫反应中的粘膜部位发挥着重要作用。 γ δ T 细胞被认为是 IL-17 产生者，但根据 CD3 表达水平，我们现在定义了具有效应记忆表型的 CD3（明亮）γ δ T 细胞子集快速产生 IL-17A（但不产生干扰素-γ）的卓越能力。 CD3(bright) gamma delta T 细胞一致表达典型种系编码的 V gamma 6/V delta 1(+) T 细胞受体。它们分布广泛，优先分布在肺部，并且在缺乏视黄酸受体相关孤儿受体 gammat 表达或内源性菌群的情况下，皮肤会受到负面影响。该群体对各种刺激做出快速反应，其机制涉及 IL-23 和 NOD 样受体家族、含有 3 (NLRP3) 炎性体依赖性 IL-1 β 的热蛋白结构域。最后，我们证明产生 IL-17 的 CD3(bright) γ δ T 细胞对肺炎球菌感染和皮肤炎症反应迅速而强烈。在这里，我们提出了一种基于 CD3 信号水平专门分析产生 IL-17 的 V gamma 6/V delta 1(+) T 细胞的新方法。使用这种门控策略，我们的数据强化了这种 γ δ T 细胞亚群在呼吸和皮肤疾病中的关键作用。
Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune responses including infection, allergy and auto-immunity. gamma delta T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3(bright) gamma delta T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-gamma. CD3(bright) gamma delta T cells uniformly express the canonical germline encoded V gamma 6/V delta 1(+) T-cell receptor. They are widely distributed with a preferential representation in the lungs and skin are negatively impacted in the absence of retinoic acid receptor-related orphan receptor gammat expression or endogenous flora. This population responded rapidly to various stimuli in a mechanism involving IL-23 and NOD-like receptor family, pyrin domain containing 3 (NLRP3)-inflammasome- dependent IL-1 beta. Finally, we demonstrated that IL-17-producing CD3(bright) gamma delta T cells responded promptly and strongly to pneumococcal infection and during skin inflammation. Here, we propose a new way to specifically analyze IL-17-producing V gamma 6/V delta 1(+) T cells based on the level of CD3 signals. Using this gating strategy, our data reinforce the crucial role of this gamma delta T-cell subset in respiratory and skin disorders.