Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq
Background: Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease. While the chemokine signaling pathway plays a pivotal role in RA pathogenesis, the specific cellular interactions remain unclear. Methods: A three-stage analytical framework was implemented. First, to uncover crucial si...
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Elsevier
2025-06-01
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| Series: | Journal of Translational Autoimmunity |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589909025000206 |
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| author | Yu Lai Zishao Zhong Runze Li Tuliang Liang Xizi He Yuan Liu Hao Yu Chuanhai Zhang Yao Xiao Liang Liu Hudan Pan |
| author_facet | Yu Lai Zishao Zhong Runze Li Tuliang Liang Xizi He Yuan Liu Hao Yu Chuanhai Zhang Yao Xiao Liang Liu Hudan Pan |
| author_sort | Yu Lai |
| collection | DOAJ |
| description | Background: Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease. While the chemokine signaling pathway plays a pivotal role in RA pathogenesis, the specific cellular interactions remain unclear. Methods: A three-stage analytical framework was implemented. First, to uncover crucial signaling pathways in RA, we conducted an analysis of bulk RNA-seq data (GSE89408) sourced from the Gene Expression Omnibus (GEO) database. Second, utilizing single-cell transcriptome data from GEO (GSE200815 and GSE152805) and EMBL's European Bioinformatics Institute (E-MTAB-8322), we delved into key cell pairs and their ligand-receptor interactions within the chemokine signaling pathway. Third, spatial transcriptome data (SDY2213) from the IMMPORT database were employed to validate the colocalization of these pivotal cell pairs. Results: Our enrichment analysis of bulk RNA-seq data underscored the chemokine signaling pathway's centrality in RA's pathogenesis. By integrating thirteen single-cell RNA sequencing datasets, we documented a notable elevation in the proportion of most lymphocyte types within RA synovium. The chemokine signaling pathway emerged as one of the primary pathways enriched in genes differentially expressed between RA and osteoarthritis in lymphocytes and CD8+ T cells. Cell-cell interaction analysis pinpointed the interaction between CD8+ T cells and endothelial cells (ECs) as a distinctive feature of the chemokine signaling pathway. Spatial transcriptome analysis further substantiated the co-localization of CD8+ T cells and ECs. Conclusions: This study highlight CD8+ T cell- EC interactions via chemokine signaling as critical drivers of RA progression, potentially promoting leukocyte transendothelial migration and synovial immune infiltration. |
| format | Article |
| id | doaj-art-0fccce2510984ab8a345edddc0b0c78f |
| institution | Kabale University |
| issn | 2589-9090 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Translational Autoimmunity |
| spelling | doaj-art-0fccce2510984ab8a345edddc0b0c78f2025-08-20T03:26:38ZengElsevierJournal of Translational Autoimmunity2589-90902025-06-011010028510.1016/j.jtauto.2025.100285Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seqYu Lai0Zishao Zhong1Runze Li2Tuliang Liang3Xizi He4Yuan Liu5Hao Yu6Chuanhai Zhang7Yao Xiao8Liang Liu9Hudan Pan10The Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; Chinese Medicine Guangdong Laboratory, Zhuhai, Guangdong Province, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; Chinese Medicine Guangdong Laboratory, Zhuhai, Guangdong Province, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; Chinese Medicine Guangdong Laboratory, Zhuhai, Guangdong Province, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, ChinaMacau Institute for Translational Medicine and Innovation, University of Macau, Macao SAR, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; Chinese Medicine Guangdong Laboratory, Zhuhai, Guangdong Province, ChinaThe Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; Chinese Medicine Guangdong Laboratory, Zhuhai, Guangdong Province, China; Corresponding author. The Second Clinical Medical School/State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.Background: Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease. While the chemokine signaling pathway plays a pivotal role in RA pathogenesis, the specific cellular interactions remain unclear. Methods: A three-stage analytical framework was implemented. First, to uncover crucial signaling pathways in RA, we conducted an analysis of bulk RNA-seq data (GSE89408) sourced from the Gene Expression Omnibus (GEO) database. Second, utilizing single-cell transcriptome data from GEO (GSE200815 and GSE152805) and EMBL's European Bioinformatics Institute (E-MTAB-8322), we delved into key cell pairs and their ligand-receptor interactions within the chemokine signaling pathway. Third, spatial transcriptome data (SDY2213) from the IMMPORT database were employed to validate the colocalization of these pivotal cell pairs. Results: Our enrichment analysis of bulk RNA-seq data underscored the chemokine signaling pathway's centrality in RA's pathogenesis. By integrating thirteen single-cell RNA sequencing datasets, we documented a notable elevation in the proportion of most lymphocyte types within RA synovium. The chemokine signaling pathway emerged as one of the primary pathways enriched in genes differentially expressed between RA and osteoarthritis in lymphocytes and CD8+ T cells. Cell-cell interaction analysis pinpointed the interaction between CD8+ T cells and endothelial cells (ECs) as a distinctive feature of the chemokine signaling pathway. Spatial transcriptome analysis further substantiated the co-localization of CD8+ T cells and ECs. Conclusions: This study highlight CD8+ T cell- EC interactions via chemokine signaling as critical drivers of RA progression, potentially promoting leukocyte transendothelial migration and synovial immune infiltration.http://www.sciencedirect.com/science/article/pii/S2589909025000206Rheumatoid arthritisSingle-cell RNA sequencingSpatial transcriptome sequencingCD8+ T cellsEndothelial cells |
| spellingShingle | Yu Lai Zishao Zhong Runze Li Tuliang Liang Xizi He Yuan Liu Hao Yu Chuanhai Zhang Yao Xiao Liang Liu Hudan Pan Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq Journal of Translational Autoimmunity Rheumatoid arthritis Single-cell RNA sequencing Spatial transcriptome sequencing CD8+ T cells Endothelial cells |
| title | Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq |
| title_full | Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq |
| title_fullStr | Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq |
| title_full_unstemmed | Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq |
| title_short | Unveiling the crucial role of CD8+ T cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk/single-cell RNA-seq |
| title_sort | unveiling the crucial role of cd8 t cell and endothelial cell interaction in rheumatoid arthritis through the integrated analysis of spatial transcriptomics and bulk single cell rna seq |
| topic | Rheumatoid arthritis Single-cell RNA sequencing Spatial transcriptome sequencing CD8+ T cells Endothelial cells |
| url | http://www.sciencedirect.com/science/article/pii/S2589909025000206 |
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