Impact of chronic alcohol exposure on conventional and regulatory murine T cell subsets.

Impact of chronic alcohol exposure on conventional and regulatory murine T cell subsets.
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慢性酒精暴露对常规和调节性小鼠 T 细胞亚群的影响。

DOI:
10.3389/fimmu.2023.1142614
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发表时间:
2023
影响因子:
7.3
通讯作者:
Ford, Mandy L.
Ford, Mandy L.
中科院分区:
医学2区
文献类型:
--
作者:
Paterson, Cameron W.;Gutierrez, Melissa B.;Coopersmith, Craig M.;Ford, Mandy L.

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慢性酒精使用对公共健康造成重大的负面影响,在其许多生物学效应中,与适应性免疫系统内的显著T细胞失调有关,尚未完全表征。用于免疫系统的高维流式细胞术分析的新型自动化策略正在迅速提高研究人员检测和表征稀有细胞类型的能力。使用慢性酒精摄入的小鼠模型结合viSNE和CITRUS分析工具,我们进行了一项机器驱动的探索性分析,比较了酒精和水喂养动物之间常规CD 4+、调节性CD 4+和CD 8 + T细胞区室中的罕见脾脏亚群。虽然大量CD 3 + T细胞、大量CD 4 + T细胞、大量CD 8 + T细胞、Foxp 3-CD 4+常规T细胞(Tconv)或Foxp 3 + CD 4+调节性T细胞(Treg)的绝对数量没有差异,但我们鉴定了慢性酒精暴露小鼠中幼稚Helios+ CD 4 +Tconv和幼稚CD 103 + CD 8+脾T细胞的数量与水喂养的对照组相比有所减少。此外,我们还鉴定了CD 69 + Treg增加和CD 103+效应调节性T细胞(eTreg)亚群减少,以及可能代表中央调节性T细胞(cTreg)和eTreg之间过渡表型的群体频率增加。这些数据提供了进一步的分辨率到已知是存在于酒精暴露的小鼠中的幼稚T细胞群减少的字符,以及描述与慢性酒精诱导的免疫功能障碍的发病机制相关的效应调节T细胞表型的改变。
Chronic alcohol use poses significant negative consequences to public health and, among its many biologic effects, is associated with significant T cell dysregulation within the adaptive immune system that has yet to be fully characterized. Novel, automated strategies for high dimensional flow cytometric analysis of the immune system are rapidly improving researchers’ ability to detect and characterize rare cell types. Using a murine model of chronic alcohol ingestion in conjunction with viSNE and CITRUS analysis tools, we performed a machine-driven, exploratory analysis comparing rare splenic subpopulations within the conventional CD4+, regulatory CD4+ and CD8+ T cell compartments between alcohol- and water-fed animals. While there were no differences in the absolute numbers of bulk CD3+ T cells, bulk CD4+ T cells, bulk CD8+ T cells, Foxp3- CD4+ conventional T cells (Tconv) or Foxp3+ CD4+ regulatory T cells (Treg), we identified populations of naïve Helios+ CD4+Tconv and naïve CD103+ CD8+ splenic T cells that were decreased in chronically alcohol exposed mice versus water-fed controls. In addition, we identified increased CD69+ Treg and decreased CD103+ effector regulatory T cell (eTreg) subsets in conjunction with increased frequency of a population that may represent a transitional phenotype between central regulatory T cell (cTreg) and eTreg. These data provide further resolution into the character of decreased naïve T cell populations known to be present in alcohol exposed mice, as well as describe alterations in effector regulatory T cell phenotypes associated with the pathogenesis of chronic alcohol-induced immune dysfunction.
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