Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS
Abstract Background Mixed connective tissue disease (MCTD) is a rare autoimmune disease, and little is known about its pathogenesis. Furthermore, MCTD, systemic lupus erythematosus (SLE), and primary Sjögren’s syndrome (pSS) share many clinical, laboratory, and immunological manifestations. This ove...
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BMC
2025-04-01
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| Online Access: | https://doi.org/10.1186/s13578-025-01374-1 |
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| author | Yanling Cui Huina Zhang Yaxuan Deng Orion Fan Junbang Wang Zhonggang Xing Jianping Tang Wenmin Zhu Bangdong Gong Yi Eve Sun |
| author_facet | Yanling Cui Huina Zhang Yaxuan Deng Orion Fan Junbang Wang Zhonggang Xing Jianping Tang Wenmin Zhu Bangdong Gong Yi Eve Sun |
| author_sort | Yanling Cui |
| collection | DOAJ |
| description | Abstract Background Mixed connective tissue disease (MCTD) is a rare autoimmune disease, and little is known about its pathogenesis. Furthermore, MCTD, systemic lupus erythematosus (SLE), and primary Sjögren’s syndrome (pSS) share many clinical, laboratory, and immunological manifestations. This overlap complicates early diagnosis and accurate treatment. Methods The transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from MCTD patients was performed using both bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) for the first time. Additionally, we applied MCTD scRNA-seq data, along with datasets from SLE (GSE135779) and pSS (GSE157278) from the Gene Expression Omnibus database, to characterize and compare the similarities and heterogeneity among MCTD, SLE, and pSS. Results We first resolved transcriptomic changes in peripheral blood immune cells of MCTD, and then revealed the shared and unique features among MCTD, SLE, and pSS. Analyses showed that the percentage of CD8+ effector T cells was increased, while mucosal-associated invariant T cells were decreased in all three diseases. Genes related to the ‘interferon (IFN) γ response’ and ‘IFN α response’ were significantly upregulated. SCENIC analysis revealed activation of STAT1 and IRF7 in disease states, targeting IFN-related genes. The IFN-II signaling network was notably elevated in all three diseases. Unique features of MCTD, SLE, and pSS were also identified. Conclusion We dissected the immune landscape of MCTD at single-cell resolution, providing new insights into the development of novel biomarkers and immunotherapies for MCTD. Furthermore, we offer insights into the transcriptomic similarities and heterogeneity across different autoimmune diseases, while highlighting prospective therapeutic targets. |
| format | Article |
| id | doaj-art-130d1ffb0cd44926b63f6c02d13b7bbd |
| institution | OA Journals |
| issn | 2045-3701 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-130d1ffb0cd44926b63f6c02d13b7bbd2025-08-20T02:28:04ZengBMCCell & Bioscience2045-37012025-04-0115111810.1186/s13578-025-01374-1Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSSYanling Cui0Huina Zhang1Yaxuan Deng2Orion Fan3Junbang Wang4Zhonggang Xing5Jianping Tang6Wenmin Zhu7Bangdong Gong8Yi Eve Sun9Stem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji UniversityStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji UniversityStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji UniversityStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji UniversityStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji UniversityStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji UniversityDivision of Rheumatology, Tongji Hospital of Tongji University School of MedicineStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji UniversityDivision of Rheumatology, Tongji Hospital of Tongji University School of MedicineStem Cell Translational Research Center, Tongji Hospital, School of Medicine, Tongji UniversityAbstract Background Mixed connective tissue disease (MCTD) is a rare autoimmune disease, and little is known about its pathogenesis. Furthermore, MCTD, systemic lupus erythematosus (SLE), and primary Sjögren’s syndrome (pSS) share many clinical, laboratory, and immunological manifestations. This overlap complicates early diagnosis and accurate treatment. Methods The transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from MCTD patients was performed using both bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) for the first time. Additionally, we applied MCTD scRNA-seq data, along with datasets from SLE (GSE135779) and pSS (GSE157278) from the Gene Expression Omnibus database, to characterize and compare the similarities and heterogeneity among MCTD, SLE, and pSS. Results We first resolved transcriptomic changes in peripheral blood immune cells of MCTD, and then revealed the shared and unique features among MCTD, SLE, and pSS. Analyses showed that the percentage of CD8+ effector T cells was increased, while mucosal-associated invariant T cells were decreased in all three diseases. Genes related to the ‘interferon (IFN) γ response’ and ‘IFN α response’ were significantly upregulated. SCENIC analysis revealed activation of STAT1 and IRF7 in disease states, targeting IFN-related genes. The IFN-II signaling network was notably elevated in all three diseases. Unique features of MCTD, SLE, and pSS were also identified. Conclusion We dissected the immune landscape of MCTD at single-cell resolution, providing new insights into the development of novel biomarkers and immunotherapies for MCTD. Furthermore, we offer insights into the transcriptomic similarities and heterogeneity across different autoimmune diseases, while highlighting prospective therapeutic targets.https://doi.org/10.1186/s13578-025-01374-1Mixed connective tissue diseaseSystemic lupus erythematosusPrimary Sjögren’s syndromeSingle-cell RNA sequencingImmune cell landscape |
| spellingShingle | Yanling Cui Huina Zhang Yaxuan Deng Orion Fan Junbang Wang Zhonggang Xing Jianping Tang Wenmin Zhu Bangdong Gong Yi Eve Sun Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS Cell & Bioscience Mixed connective tissue disease Systemic lupus erythematosus Primary Sjögren’s syndrome Single-cell RNA sequencing Immune cell landscape |
| title | Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS |
| title_full | Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS |
| title_fullStr | Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS |
| title_full_unstemmed | Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS |
| title_short | Shared and distinct peripheral blood immune cell landscape in MCTD, SLE, and pSS |
| title_sort | shared and distinct peripheral blood immune cell landscape in mctd sle and pss |
| topic | Mixed connective tissue disease Systemic lupus erythematosus Primary Sjögren’s syndrome Single-cell RNA sequencing Immune cell landscape |
| url | https://doi.org/10.1186/s13578-025-01374-1 |
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