Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis
Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis
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DOI：
10.1038/s41598-019-55852-x
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发表时间：
2019-12-19
影响因子：
4.6
通讯作者：
Priller, Josef
中科院分区：
文献类型：
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作者：
Boettcher, Chotima;Fernandez-Zapata, Camila;Priller, Josef
多发性硬化症(MS)是一种炎症性脱髓鞘和中枢神经系统退行性疾病。在啮齿动物模型中的研究表明，中枢神经系统浸润性单核细胞来源的巨噬细胞与疾病严重程度有关。然而，人们对人类知之甚少。在这里，我们使用多路单细胞质量细胞术和基于算法的数据分析，对从健康对照组和早期MS药物初治患者分离的外周血单核细胞(PBMC)进行了探索性分析。设计了两个由抗体组成的抗体小组，以综合分析不同的免疫细胞群体，特别是单核细胞。两组间PBMC组成和标志物表达总体相似。但早期MS-PBMC中CCR7(+)和IL-6(+)T细胞增多，而NFAT1(Hi)T-bet(Hi)CD4(+)T细胞减少。同样，我们检测到了人类白细胞抗原DR+淋巴细胞室中CCR7+和MIPβ亚群组成的变化。早期MS患者单核/髓系细胞仅有轻微改变，即CD141(Hi)IRF8(Hi)CXCR3(+)CD68(-)树突状细胞丰度降低。与克罗恩病不同，早期MS患者的单核细胞比例与健康对照组相比没有显著差异。这项研究为今后研究MS患者不同的PBMC亚群提供了有价值的资源。
Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Studies in rodent models demonstrated an association of CNS-infiltrating monocyte-derived macrophages with disease severity. However, little is known about humans. Here, we performed an exploratory analysis of peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and drug-naive patients with early MS using multiplexed single-cell mass cytometry and algorithm-based data analysis. Two antibody panels comprising a total of 64 antibodies were designed to comprehensively analyse diverse immune cell populations, with particular emphasis on monocytes. PBMC composition and marker expression were overall similar between the groups. However, an increased abundance of CCR7(+) and IL-6(+) T cells was detected in early MS-PBMCs, whereas NFAT1(hi)T-bet(hi)CD4(+) T cells were decreased. Similarly, we detected changes in the subset composition of the CCR7+ and MIP beta hi HLA-DR+ lymphocyte compartment. Only mild alterations were detected in monocytes/myeloid cells of patients with early MS, namely a decreased abundance of CD141(hi)IRF8(hi)CXCR3(+)CD68(-) dendritic cells. Unlike in Crohn's disease, no significant differences were found in the monocyte fraction of patients with early MS compared to healthy controls. This study provides a valuable resource for future studies designed to characterise and target diverse PBMC subsets in MS.