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Correlation of Prof...
Correlation of Professional Antigen-Presenting Tbet+CD11c+ B Cells With Bone Destruction in Untreated Rheumatoid Arthritis
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- McGrath, Sarah, 1993 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Grimstad, Kristoffer (author)
- Gothenburg University,Göteborgs universitet,Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden,Infection Biology,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Thorarinsdottir, Katrin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Forslind, Kristina (author)
- Halmstad University,Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Spenshults artrit grupp,Forskargrupper vid Lunds universitet,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Spenshults arthritis group,Lund University Research Groups
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- Glinatsi, Daniel (author)
- Skaraborg Hospital, Skövde, Sweden
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- Leu Agelii, Monica, 1977 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Aranburu, Alaitz (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Sundell, Timothy, 1992 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Jonsson, Charlotte A. (author)
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Camponeschi, Alessandro (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Hultgård Ekwall, Anna-Karin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Tilevik, Andreas (author)
- University of Skövde,Högskolan i Skövde,Institutionen för biovetenskap,Forskningsmiljön Systembiologi,Infection Biology
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- Gjertsson, Inger, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Mårtensson, Inga-Lill, 1957 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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(creator_code:org_t)
- John Wiley & Sons, 2024
- 2024
- English.
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In: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 76:8, s. 1263-1277
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Abstract
Subject headings
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- Objective: Subsets of CD21−/low memory B cells (MBCs), including double-negative (DN, CD27−IgD−) and Tbet+CD11c+ cells, are expanded in chronic inflammatory diseases. In rheumatoid arthritis (RA), CD21−/low MBCs correlate with joint destruction. However, whether this is due to the Tbet+CD11c+ subset, its function and pathogenic contribution to RA are unknown. This study aims to investigate the association between CD21−/lowTbet+CD11c+ MBCs and joint destruction as well as other clinical parameters and to elucidate their functional properties in patients with untreated RA (uRA). Methods: Clinical observations were combined with flow cytometry (n = 36) and single-cell RNA sequencing (scRNA-seq) and V(D)J sequencing (n = 4) of peripheral blood (PB) MBCs from patients with uRA. The transcriptome of circulating Tbet+CD11c+ MBCs was compared with scRNA-seq data of synovial B cells. In vitro coculture of Tbet+CD11c+ B cells with T cells was used to assess costimulatory capacity. Results: CD21−/lowTbet+CD11c+ MBCs in PB correlated with bone destruction but no other clinical parameters analyzed. The Tbet+CD11c+ MBCs have undergone clonal expansion and express somatically mutated V genes. Gene expression analysis of these cells identified a unique signature of more than 150 up-regulated genes associated with antigen presentation functions, including B cell receptor activation and clathrin-mediated antigen internalization; regulation of actin filaments, endosomes, and lysosomes; antigen processing, loading, presentation, and costimulation; a transcriptome mirrored in their synovial tissue counterparts. In vitro, Tbet+CD11c+ B cells induced retinoic acid receptor–related orphan nuclear receptor γT expression in CD4+ T cells, thereby polarizing to Th17 cells, a T cell subset critical for osteoclastogenesis and associated with bone destruction. Conclusion: This study suggests that Tbet+CD11c+ MBCs contribute to the pathogenesis of RA by promoting bone destruction through antigen presentation, T cell activation, and Th17 polarization. (Figure presented.).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Infection Biology
- Infektionsbiologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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McGrath, Sarah, ...
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Grimstad, Kristo ...
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Thorarinsdottir, ...
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Forslind, Kristi ...
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Glinatsi, Daniel
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Leu Agelii, Moni ...
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Aranburu, Alaitz
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Sundell, Timothy ...
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Jonsson, Charlot ...
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Camponeschi, Ale ...
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Hultgård Ekwall, ...
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Tilevik, Andreas
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Gjertsson, Inger ...
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Mårtensson, Inga ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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MEDICAL AND HEAL ...
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MEDICAL AND HEAL ...
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Arthritis & Rheu ...
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University of Skövde
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Lund University
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University of Gothenburg