Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4(+) T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren's Syndrome.
Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4(+) T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren's Syndrome.
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单细胞 RNA 测序揭示了原发性干燥综合征中细胞毒性 CD4 T 淋巴细胞的扩增和免疫细胞的情况
DOI：
10.3389/fimmu.2020.594658
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发表时间：
2020
影响因子：
7.3
通讯作者：
Yang M
中科院分区：
文献类型：
--
作者：
Hong X;Meng S;Tang D;Wang T;Ding L;Yu H;Li H;Liu D;Dai Y;Yang M
原发性干燥综合征(PSS)是一种全身性自身免疫性疾病，其发病机制尚不清楚。在这项研究中，我们旨在探索导致该病发病的细胞和分子机制。我们对5名PSS患者和5名健康对照的57,288个外周血单核细胞(PBMC)进行了单细胞RNA测序(scRNA-seq)。分析参与PSS发病的免疫细胞亚群和易感基因。用流式细胞仪对scRNA-seq结果进行验证。我们发现两个亚群在PSS患者中显著扩大。其中一个高表达的细胞毒基因被命名为CD4+CTL细胞毒性T淋巴细胞，另一个高表达的T细胞受体(TCR)可变基因被命名为CD4+TRAV13-2+T细胞。流式细胞仪检测结果显示，10例pSS患者外周血中CD_4~+、GZMB~+细胞百分率明显高于正常对照组(P=0.008)。PSS患者巨噬细胞IL-1β、B细胞TCL1a及大部分细胞亚群干扰素反应基因表达水平上调。PSS患者HLADRB5、CTLA4、AQP3等易感基因高表达。我们的数据揭示了疾病特异性免疫细胞亚群，并提供了一些潜在的PSS新靶点。CD4+CTL的特异性扩增可能参与了PSS的发病机制，这可能为PSS的治疗干预提供有价值的启示。
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, and its pathogenetic mechanism is far from being understood. In this study, we aimed to explore the cellular and molecular mechanisms that lead to pathogenesis of this disease. We applied single-cell RNA sequencing (scRNA-seq) to 57,288 peripheral blood mononuclear cells (PBMCs) from five patients with pSS and five healthy controls. The immune cell subsets and susceptibility genes involved in the pathogenesis of pSS were analyzed. Flow cytometry was preformed to verify the result of scRNA-seq. We identified two subpopulations significantly expand in pSS patients. The one highly expressing cytotoxicity genes is named as CD4+ CTLs cytotoxic T lymphocyte, and another highly expressing T cell receptor (TCR) variable gene is named as CD4+ TRAV13-2+ T cell. Flow cytometry results showed the percentages of CD4+ CTLs, which were profiled with CD4+ and GZMB+ staining; the total T cells of 10 patients with pSS were significantly higher than those of 10 healthy controls (P= 0.008). The expression level of IL-1β in macrophages, TCL1A in B cells, as well as interferon (IFN) response genes in most cell subsets was upregulated in the patients with pSS. Susceptibility genes including HLA-DRB5, CTLA4, and AQP3 were highly expressed in patients with pSS. Our data revealed disease-specific immune cell subsets and provided some potential new targets of pSS. Specific expansion of CD4+ CTLs may be involved in the pathogenesis of pSS, which might give valuable insights for therapeutic interventions of pSS.
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影响因子：
64.5
作者：
Levine JH;Simonds EF;Bendall SC;Davis KL;Amir el-AD;Tadmor MD;Litvin O;Fienberg HG;Jager A;Zunder ER;Finck R;Gedman AL;Radtke I;Downing JR;Pe'er D;Nolan GP
通讯作者：
Nolan GP
影响因子：
4.6
作者：
Maehara T;Moriyama M;Hayashida JN;Tanaka A;Shinozaki S;Kubo Y;Matsumura K;Nakamura S
通讯作者：
Nakamura S
影响因子：
5.5
作者：
Jasiek, Magali;Karras, Alexandre;Terrier, Benjamin
通讯作者：
Terrier, Benjamin
影响因子：
21.3
作者：
Gao, Shuai;Yan, Liying;Tang, Fuchou
通讯作者：
Tang, Fuchou
影响因子：
3.4
作者：
Delporte, Christine;Steinfeld, Serge
通讯作者：
Steinfeld, Serge