دورية أكاديمية
Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.
العنوان: | Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium. |
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المؤلفون: | Dunlap G; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Wagner A; Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA., Meednu N; Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA., Wang R; Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA., Zhang F; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Division of Rheumatology and the Center for Health Artificial Intelligence, University of Colorado School of Medicine, Aurora, CO, USA., Ekabe JC; Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA., Jonsson AH; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Wei K; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Sakaue S; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Nathan A; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Bykerk VP; Hospital for Special Surgery, New York, NY, USA.; Weill Cornell Medicine, New York, NY, USA., Donlin LT; Hospital for Special Surgery, New York, NY, USA.; Weill Cornell Medicine, New York, NY, USA., Goodman SM; Hospital for Special Surgery, New York, NY, USA.; Weill Cornell Medicine, New York, NY, USA., Firestein GS; Division of Rheumatology, Allergy and Immunology, University of California, San Diego;, La Jolla, CA, USA., Boyle DL; Division of Rheumatology, Allergy and Immunology, University of California, San Diego;, La Jolla, CA, USA., Holers VM; Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA., Moreland LW; Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.; Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Tabechian D; Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA., Pitzalis C; Centre for Experimental Medicine & Rheumatology, EULAR Centre of Excellence, William Harvey Research Institute, Queen Mary University of London, London, UK.; Barts Health NHS Trust, Barts Biomedical Research Centre (BRC), National Institute for Health and Care Research (NIHR), London, UK.; Department of Biomedical Sciences, Humanitas University and Humanitas Research Hospital, Milan, Italy., Filer A; Rheumatology Research Group, Institute for Inflammation and Ageing, University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.; Birmingham Tissue Analytics, Institute of Translational Medicine, University of Birmingham, Birmingham, UK.; NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK., Raychaudhuri S; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA.; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Brenner MB; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Thakar J; Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.; Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA., McDavid A; Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA., Rao DA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. darao@bwh.harvard.edu., Anolik JH; Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, USA. jennifer_anolik@urmc.rochester.edu.; Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. jennifer_anolik@urmc.rochester.edu. |
مؤلفون مشاركون: | Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network |
المصدر: | Nature communications [Nat Commun] 2024 Jun 11; Vol. 15 (1), pp. 4991. Date of Electronic Publication: 2024 Jun 11. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
مواضيع طبية MeSH: | Arthritis, Rheumatoid*/immunology , Arthritis, Rheumatoid*/metabolism , Arthritis, Rheumatoid*/genetics , Arthritis, Rheumatoid*/pathology , Synovial Membrane*/immunology , Synovial Membrane*/metabolism , B-Lymphocytes*/immunology , B-Lymphocytes*/metabolism, Humans ; Female ; Male ; Middle Aged ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Lymphocyte Subsets/immunology ; Lymphocyte Subsets/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Single-Cell Analysis ; Transcriptome ; Plasma Cells/immunology ; Plasma Cells/metabolism ; Aged ; Lymphocyte Activation ; Adult |
مستخلص: | Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA. (© 2024. The Author(s).) |
التعليقات: | Update of: bioRxiv. 2023 Mar 21:2023.03.18.533282. doi: 10.1101/2023.03.18.533282. (PMID: 36993527) |
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معلومات مُعتمدة: | UH2 AR067685 United States AR NIAMS NIH HHS; UM2 AR067678 United States AR NIAMS NIH HHS; K08 AR081412 United States AR NIAMS NIH HHS; UH2 AR067681 United States AR NIAMS NIH HHS; UH2 AR067688 United States AR NIAMS NIH HHS; UH2 AR067689 United States AR NIAMS NIH HHS; UH2 AR067690 United States AR NIAMS NIH HHS; UH2 AR067677 United States AR NIAMS NIH HHS; UH2 AR067694 United States AR NIAMS NIH HHS; UH2 AR067679 United States AR NIAMS NIH HHS; UH2 AR067676 United States AR NIAMS NIH HHS; UH2 AR067691 United States AR NIAMS NIH HHS |
فهرسة مساهمة: | Investigator: J Albrecht; W Apruzzese; JL Barnas; JM Bathon; A Ben-Artzi; BF Boyce; SL Bridges; D Campbell; HL Carr; A Ceponis; A Chicoine; A Cordle; M Curtis; KD Deane; E DiCarlo; P Dunn; L Forbess; L Geraldino-Pardilla; EM Gravallese; PK Gregersen; JM Guthridge; D Horowitz; LB Hughes; K Ishigaki; LB Ivashkiv; JA James; JB Kang; G Keras; I Korsunsky; A Lakhanpal; JA Lederer; Y Li; ZJ Li; KP Liao; H Maecker; AM Mandelin; I Mantel; M Maybury; MJ McGeachy; J Mears; A Nerviani; DE Orange; H Perlman; J Rangel-Moreno; K Raza; Y Reshef; C Ritchlin; F Rivellese; WH Robinson; L Rumker; I Sahbudin; K Salomon-Escoto; D Scheel-Toellner; JA Seifert; A Singaraju; MH Smith; PJ Utz; K Weinand; D Weisenfeld; MH Weisman; Q Xiao; Z Zhu |
تواريخ الأحداث: | Date Created: 20240611 Date Completed: 20240611 Latest Revision: 20240725 |
رمز التحديث: | 20240726 |
مُعرف محوري في PubMed: | PMC11167034 |
DOI: | 10.1038/s41467-024-49186-0 |
PMID: | 38862501 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-024-49186-0 |