IL-12信号传导驱动TH1衍生的TFH1样细胞群体的分化和功能。,Scientific Reports

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IL-12信号传导驱动TH1衍生的TFH1样细胞群体的分化和功能。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-09-30 , DOI: 10.1038/s41598-019-50614-1
Michael D Powell ₁ , Kaitlin A Read _{1,

2,

3} , Bharath K Sreekumar _{1,

4} , Devin M Jones _{1,

4} , Kenneth J Oestreich _{1,

2,

5}

Affiliation

CD4 + T滤泡辅助细胞（TFH）为B细胞提供帮助，并促进抗体介导的免疫反应。越来越多的证据支持TFH种群的存在，这些TFH种群分泌通常与其他CD4 + T细胞亚群的效应子功能相关的细胞因子。其中包括偏向T辅助1（TH1）的TFH（TFH1）细胞，这些细胞在对病原体的免疫反应以及自身免疫性疾病的发病机理中均具有公认的作用。鉴于它们对人类健康的明显重要性，因此有兴趣了解调节TFH1细胞形成和功能的机制。但是，它们的来源和分化的分子要求尚不清楚。在这里，我们描述了鼠TH1衍生的种群，表达趋化因子受体Cxcr3并产生TH1细胞因子干扰素γ和TFH相关细胞因子白介素21（IL-21）的TFH1样细胞。此外，这些TFH1样细胞以与常规IL-6衍生的TFH样细胞无法区分的水平促进B细胞活化和抗体产生。关于它们的调节要求，我们发现IL-12信号对于这种TFH1样细胞群的分化和功能是必需的。具体而言，依赖IL-12的STAT4激活，而出乎意料的是STAT3，可促进TFH1样细胞中IL-21和TFH谱系定义转录因子Bcl-6的表达增加。综上所述，这些发现为TFH1细胞的潜在来源和分化需求提供了见识。这些TFH1样细胞以与传统IL-6衍生的TFH样细胞无法区分的水平促进B细胞活化和抗体产生。关于它们的调节要求，我们发现IL-12信号对于这种TFH1样细胞群的分化和功能是必需的。具体而言，依赖IL-12的STAT4激活，而出乎意料的是STAT3，可促进TFH1样细胞中IL-21和TFH谱系定义转录因子Bcl-6的表达增加。综上所述，这些发现为TFH1细胞的潜在起源和分化需求提供了见识。这些TFH1样细胞以与传统IL-6衍生的TFH样细胞无法区分的水平促进B细胞活化和抗体产生。关于它们的调节要求，我们发现IL-12信号对于这种TFH1样细胞群的分化和功能是必需的。具体而言，依赖IL-12的STAT4激活，而出乎意料的是STAT3，可促进TFH1样细胞中IL-21和TFH谱系定义转录因子Bcl-6的表达增加。综上所述，这些发现为TFH1细胞的潜在起源和分化需求提供了见识。我们发现，IL-12信号传导对于这种TFH1样细胞群体的分化和功能是必需的。具体而言，依赖IL-12的STAT4激活，而出乎意料的是STAT3，可促进TFH1样细胞中IL-21和TFH谱系定义转录因子Bcl-6的表达增加。综上所述，这些发现为TFH1细胞的潜在来源和分化需求提供了见识。我们发现，IL-12信号传导对于这种TFH1样细胞群体的分化和功能是必需的。具体而言，依赖IL-12的STAT4激活，而出乎意料的是STAT3，可促进TFH1样细胞中IL-21和TFH谱系定义转录因子Bcl-6的表达增加。综上所述，这些发现为TFH1细胞的潜在起源和分化需求提供了见识。

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IL-12 signaling drives the differentiation and function of a TH1-derived TFH1-like cell population.

CD4+ T follicular helper (TFH) cells provide help to B cells and promote antibody-mediated immune responses. Increasing evidence supports the existence of TFH populations that secrete cytokines typically associated with the effector functions of other CD4+ T cell subsets. These include T helper 1 (TH1)-biased TFH (TFH1) cells that have recognized roles in both immune responses to pathogens and also the pathogenesis of autoimmune disease. Given their apparent importance to human health, there is interest in understanding the mechanisms that regulate TFH1 cell formation and function. However, their origin and the molecular requirements for their differentiation are unclear. Here, we describe a population of murine TH1-derived, TFH1-like cells that express the chemokine receptor Cxcr3 and produce both the TH1 cytokine interferon-γ and the TFH-associated cytokine interleukin-21 (IL-21). Furthermore, these TFH1-like cells promote B cell activation and antibody production at levels indistinguishable from conventional IL-6-derived TFH-like cells. Regarding their regulatory requirements, we find that IL-12 signaling is necessary for the differentiation and function of this TFH1-like cell population. Specifically, IL-12-dependent activation of STAT4, and unexpectedly STAT3, promotes increased expression of IL-21 and the TFH lineage-defining transcription factor Bcl-6 in TFH1-like cells. Taken together, these findings provide insight into the potential origin and differentiation requirements of TFH1 cells.

更新日期：2019-09-30

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