Circulating Factors in Trauma Plasma Activate Specific Human Immune Cell Subsets
Circulating Factors in Trauma Plasma Activate Specific Human Immune Cell Subsets
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DOI：
10.1016/j.injury.2020.03.009
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发表时间：
2020-04-01
影响因子：
2.5
通讯作者：
Lederer, James A.
中科院分区：
文献类型：
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作者：
Cahill, Laura A.;Guo, Fei;Lederer, James A.
背景：创伤导致组织损伤，导致损伤相关分子模式(DAMP)和其他介质在损伤部位和全身释放。这些介质扰乱免疫系统的动态平衡，并可能激活多细胞免疫反应，导致下游并发症，如感染和败血症的发展。为了确定这些变化的特征，我们使用光时间质谱仪来确定创伤血浆如何影响正常的外周血单核细胞(PBMC)激活，以深入了解创伤诱导的循环因子对人类免疫细胞群体的动力学和性质。更好地了解创伤中激活细胞的成分可能有助于发现治疗靶点。方法：将健康志愿者的PBMC与5%的血浆(健康、创伤-1天或创伤-3天)或已知的湿组织培养24小时，样本用免疫表型细胞-TOF抗体板染色。结果：创伤患者第1天血浆可诱导CD11c+NK细胞和CD73+/CCR7+CD8 T细胞亚群的急性扩增，而第3天创伤患者血浆未见明显差异。此外，创伤血浆没有诱导CD4+T细胞的增殖，但确实引起了表型向CD38+/CCR7+表达的CD4+T细胞的转变。Luminex对细胞因子的多重分析显示，创伤后第1天血浆中IL-IRA、IL-6和IL-15水平升高。与创伤第1天血浆相似，已知丹参的PBMC刺激显示CD11c+NK细胞的激活和扩增。结论：我们假设创伤血浆中的循环因子可以诱导正常人免疫细胞亚群的表型激活。使用一种公正的方法，我们确定了对创伤血浆有反应的免疫细胞亚群的特定变化。此外，CD11c+NK细胞对DAMPS和内毒素也有反应，这表明它们可能也对创伤血浆中类似的成分有反应。总的来说，我们的数据表明正常的PBMC对创伤血浆的反应涉及特定的NK和CD8+T细胞亚群的显著变化。未来的研究将针对这些创伤血浆反应性免疫细胞亚群的功能。这些发现对急性创伤损伤领域具有重要意义。爱思唯尔有限公司出版。
Background: Trauma causes tissue injury that results in the release of damage associated molecular patterns (DAMPs) and other mediators at the site of injury and systemically. Such mediators disrupt immune system homeostasis and may activate multicellular immune responses with downstream complications such as the development of infections and sepsis. To characterize these alterations, we used time-of-light mass cytometry to determine how trauma plasma affects normal peripheral blood mononuclear cell (PBMC) activation to gain insights into the kinetics and nature of trauma-induced circulating factors on human immune cell populations. A better understanding of the components that activate cells in trauma may aid in the discovery of therapeutic targets.Methods: PBMCs from healthy volunteers were cultured with 5% plasma (healthy, trauma-1 day, or trauma-3day) or known DAMPs for 24 h. Samples were stained with a broad immunophenotyping CyTOF antibody panel. Multiplex (Luminex) cytokine assays were used to measure differences in multiple cytokine levels in healthy and trauma plasma samples.Results: Plasma from day 1, but not day 3 trauma patients induced the acute expansion of CD11c+ NK cells and CD73+/CCR7+ CD8 T cell subpopulations. Additionally, trauma plasma did not induce CD4+ T cell expansion but did cause a phenotypic shift towards CD38+/CCR7+ expressing CD4+ T cells. Multiplex analysis of cytokines by Luminex showed increased levels of IL-IRA, IL-6 and IL-15 in trauma-1day plasma. Similar to trauma day 1 plasma, PBMC stimulation with known DAMPs showed activation and expansion of CD11c+ NK cells.Conclusions: We hypothesized that circulating factors in trauma plasma would induce phenotypic activation of normal human immune cell subsets. Using an unbiased approach, we identified specific changes in immune cell subsets that respond to trauma plasma. Additionally, CD11c+ NK cells expanded in response to DAMPs and LPS, suggesting they may also be responding to similar components in trauma plasma. Collectively, our data demonstrate that the normal PBMC response to trauma plasma involves marked changes in specific subsets of NK and CD8+ T cell populations. Future studies will target the function of these trauma plasma reactive immune cell subsets. These findings have important implications for the field of acute traumatic injuries. Published by Elsevier Ltd.