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.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40212397", "kind": "science-record", "revision": 4, "content_hash": "sha256:53434980c6870560839b4f188b43e5ef469b83f74c7924057e033720ef0e5142", "created_at": "2026-11-01T20:30:23Z", "updated_at": "2026-11-01T22:56:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "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.", "doi": "10.1016/j.jtauto.2025.100285", "pmid": "40212397", "authors": ["Yu Lai", "Zishao Zhong", "Runze Li", "Tuliang Liang", "Xizi He", "Yuan Liu", "Hao Yu", "Chuanhai Zhang", "Yao Xiao", "Liang Liu", "Hudan Pan"], "journal": "Journal of translational autoimmunity", "year": 2025, "abstract": "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.\nMethods: 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.\nResults: 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.\nConclusions: 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.", "claims": [{"id": "claim-method", "statement": "DEGs in the scRNA-seq data was detected by Wilcoxon rank sum test. Other data were statistically analyzed using Student's t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40212397", "locator": "sections[11] \"Statistical analysis\" paragraph 2", "quote": "DEGs in the scRNA-seq data was detected by Wilcoxon rank sum test. Other data were statistically analyzed using Student's t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All the data I used in my research came from some database repositorys and was described in the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40212397", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "All the data I used in my research came from some database repositorys and was described in the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using the edgeR package and the Wilcoxon test, we identified 1009 DEGs between the OA and RA groups in GSE89408 (Fig. 1A).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40212397", "locator": "sections[13] \"Identification of DEGs and functional enrichment analysis from bulk RNA-seq\" paragraph 2", "quote": "Using the edgeR package and the Wilcoxon test, we identified 1009 DEGs between the OA and RA groups in GSE89408 (Fig. 1A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Using the edgeR package and the Wilcoxon test, we identified 1009 DEGs between the OA and RA groups in GSE89408 (Fig. 1A).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40212397"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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By integrating thirteen single-cell RNA sequencing datasets, we documented a notable elevation", "sing the R package clusterProfiler (V4.8.3). Single-cell RNA-seq data processing We downloaded three files—ba", "ction [36]. Statistical analysis DEGs in the scRNA-seq data was detected by Wilcoxon rank sum test."], "order_basis": "paper_text_order:122", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["spatial transcriptomics and bulk/single-cell RNA-seq.", "ways in RA, we conducted an analysis of bulk RNA-seq data (GSE89408) sourced from the Gene Expres", "rs. Results: Our enrichment analysis of bulk RNA-seq data underscored the chemokine signaling pat", "genesis. 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