Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome
ObjectivePrimary 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.MethodsWe applied single-cell RNA sequencing (sc...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.594658/full |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Xiaoping Hong Xiaoping Hong Shuhui Meng Donge Tang Tingting Wang Liping Ding Haiyan Yu Heng Li Dongzhou Liu Yong Dai Min Yang |
| spellingShingle |
Xiaoping Hong Xiaoping Hong Shuhui Meng Donge Tang Tingting Wang Liping Ding Haiyan Yu Heng Li Dongzhou Liu Yong Dai Min Yang Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome Frontiers in Immunology primary Sjögren’s syndrome single-cell RNA sequencing CD4+ cytotoxic T lymphocytes TCL1A susceptibility genes |
| author_facet |
Xiaoping Hong Xiaoping Hong Shuhui Meng Donge Tang Tingting Wang Liping Ding Haiyan Yu Heng Li Dongzhou Liu Yong Dai Min Yang |
| author_sort |
Xiaoping Hong |
| title |
Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome |
| title_short |
Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome |
| title_full |
Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome |
| title_fullStr |
Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome |
| title_full_unstemmed |
Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s Syndrome |
| title_sort |
single-cell rna sequencing reveals the expansion of cytotoxic cd4+ t lymphocytes and a landscape of immune cells in primary sjögren’s syndrome |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2021-02-01 |
| description |
ObjectivePrimary 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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. |
| topic |
primary Sjögren’s syndrome single-cell RNA sequencing CD4+ cytotoxic T lymphocytes TCL1A susceptibility genes |
| url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.594658/full |
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doaj-d555f8c9f066443bbb5176fb327d7cec2021-02-02T05:07:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.594658594658Single-Cell RNA Sequencing Reveals the Expansion of Cytotoxic CD4+ T Lymphocytes and a Landscape of Immune Cells in Primary Sjögren’s SyndromeXiaoping Hong0Xiaoping Hong1Shuhui Meng2Donge Tang3Tingting Wang4Liping Ding5Haiyan Yu6Heng Li7Dongzhou Liu8Yong Dai9Min Yang10Department of Rheumatology and Immunology, Southern Medical University, Nanfang Hospital, Guangzhou, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen People’s Hospital (The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology), Shenzhen, ChinaDepartment of Rheumatology and Immunology, Southern Medical University, Nanfang Hospital, Guangzhou, ChinaObjectivePrimary 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2020.594658/fullprimary Sjögren’s syndromesingle-cell RNA sequencingCD4+ cytotoxic T lymphocytesTCL1Asusceptibility genes |