Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome
Objective: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with an unclear pathogenetic mechanism in the labial gland. This study aims to investigate the cellular and molecular mechanisms contributing to the development of this disease. Methods: Single-cell RNA sequencing (sc...
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Elsevier
2024-12-01
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| Series: | Journal of Translational Autoimmunity |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589909024000182 |
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| author | Jun Huang Jia Tang Chen Zhang Tingting Liu Zhiyong Deng Lei Liu |
| author_facet | Jun Huang Jia Tang Chen Zhang Tingting Liu Zhiyong Deng Lei Liu |
| author_sort | Jun Huang |
| collection | DOAJ |
| description | Objective: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with an unclear pathogenetic mechanism in the labial gland. This study aims to investigate the cellular and molecular mechanisms contributing to the development of this disease. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on 32,337 cells of labial glands from three pSS patients and three healthy individuals. We analyzed all cell subsets implicated in pSS pathogenesis. Results: Our research revealed diminished differentiation among epithelial cells, concomitant with an enhancement of interferons (IFNs)-mediated signaling pathways. This indicates a cellular functional shift in reaction to inflammatory triggers. Moreover, we observed an augmentation in the population of myofibroblasts and endothelial cells, likely due to the intensified IFNs signaling, suggesting a possible reconfiguration of tissue structure and vascular networks in the impacted regions. Within the immune landscape, there was an apparent increase in immunosuppressive macrophages and dendritic cells (DCs), pointing to an adaptive immune mechanism aimed at modulating inflammation and averting excessive tissue harm. Elevated activation levels of CD4+T cells, along with a rise in regulatory T (Treg) cells, were noted, indicating a nuanced immune interplay designed to manage the inflammatory response. In the CD8+T cell subsests, we detected a notable increase in cells expressing granzyme K (GZMK), signaling an intensified cytotoxic activity. Additionally, the escalated presence of T cells with high levels of heat shock proteins (HSPs) suggests a cellular stress condition, possibly associated with persistent low-grade inflammation, mirroring the chronic aspect of the condition. Conclusions: Our research identified distinct stromal and immune cell populations linked to pSS, revealing new potential targets for its management. The activation of myeloid, B, and T cells could contribute to pSS pathogenesis, providing important guidance for therapeutic approaches. |
| format | Article |
| id | doaj-art-4508f073f6f84faeab0954d27b08efee |
| institution | Kabale University |
| issn | 2589-9090 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Translational Autoimmunity |
| spelling | doaj-art-4508f073f6f84faeab0954d27b08efee2024-12-13T11:00:44ZengElsevierJournal of Translational Autoimmunity2589-90902024-12-019100248Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndromeJun Huang0Jia Tang1Chen Zhang2Tingting Liu3Zhiyong Deng4Lei Liu5Department of Rheumatology and Immunology, The First People’s Hospital of Kunshan, Jiangsu, Suzhou, 215300, ChinaDepartment of Rheumatology and Immunology, The First People’s Hospital of Kunshan, Jiangsu, Suzhou, 215300, ChinaDepartment of Rheumatology and Immunology, The First People’s Hospital of Kunshan, Jiangsu, Suzhou, 215300, ChinaDepartment of Rheumatology and Immunology, The First People’s Hospital of Kunshan, Jiangsu, Suzhou, 215300, ChinaCorresponding author. Department of Rheumatology and Immunology, the First People’s Hospital of Kunshan, Jiangsu, Suzhou, 215300, China.; Department of Rheumatology and Immunology, The First People’s Hospital of Kunshan, Jiangsu, Suzhou, 215300, ChinaCorresponding author. Department of Rheumatology and Immunology, the First People’s Hospital of Kunshan, Jiangsu, Suzhou, 215300, China.; Department of Rheumatology and Immunology, The First People’s Hospital of Kunshan, Jiangsu, Suzhou, 215300, ChinaObjective: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with an unclear pathogenetic mechanism in the labial gland. This study aims to investigate the cellular and molecular mechanisms contributing to the development of this disease. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on 32,337 cells of labial glands from three pSS patients and three healthy individuals. We analyzed all cell subsets implicated in pSS pathogenesis. Results: Our research revealed diminished differentiation among epithelial cells, concomitant with an enhancement of interferons (IFNs)-mediated signaling pathways. This indicates a cellular functional shift in reaction to inflammatory triggers. Moreover, we observed an augmentation in the population of myofibroblasts and endothelial cells, likely due to the intensified IFNs signaling, suggesting a possible reconfiguration of tissue structure and vascular networks in the impacted regions. Within the immune landscape, there was an apparent increase in immunosuppressive macrophages and dendritic cells (DCs), pointing to an adaptive immune mechanism aimed at modulating inflammation and averting excessive tissue harm. Elevated activation levels of CD4+T cells, along with a rise in regulatory T (Treg) cells, were noted, indicating a nuanced immune interplay designed to manage the inflammatory response. In the CD8+T cell subsests, we detected a notable increase in cells expressing granzyme K (GZMK), signaling an intensified cytotoxic activity. Additionally, the escalated presence of T cells with high levels of heat shock proteins (HSPs) suggests a cellular stress condition, possibly associated with persistent low-grade inflammation, mirroring the chronic aspect of the condition. Conclusions: Our research identified distinct stromal and immune cell populations linked to pSS, revealing new potential targets for its management. The activation of myeloid, B, and T cells could contribute to pSS pathogenesis, providing important guidance for therapeutic approaches.http://www.sciencedirect.com/science/article/pii/S2589909024000182Labial glandSjögren's syndromescRNA-seqMicroenvironment |
| spellingShingle | Jun Huang Jia Tang Chen Zhang Tingting Liu Zhiyong Deng Lei Liu Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome Journal of Translational Autoimmunity Labial gland Sjögren's syndrome scRNA-seq Microenvironment |
| title | Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome |
| title_full | Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome |
| title_fullStr | Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome |
| title_full_unstemmed | Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome |
| title_short | Single-cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary Sjögren's syndrome |
| title_sort | single cell transcriptomic analysis uncovers heterogeneity in the labial gland microenvironment of primary sjogren s syndrome |
| topic | Labial gland Sjögren's syndrome scRNA-seq Microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2589909024000182 |
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