CXCR5/CXCL13 pathway, a key driver for migration of regulatory B10 cells, is defective in patients with rheumatoid arthritis
| Autor: | J. Mielle, Pierre Corbeau, Kristina Schreiber, R. Audo, Laurence Macia, Jacques Morel, Claire Daien, Bernard Combe, Claire Rempenault |
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| Přispěvatelé: | MORNET, Dominique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), The University of Sydney, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2021 |
| Předmět: |
Receptors
CXCR5 Chemokine [SDV]Life Sciences [q-bio] Regulatory B cells Cell chemical and pharmacologic phenomena Inflammation Arthritis Rheumatoid 03 medical and health sciences 0302 clinical medicine Rheumatology Synovial Fluid medicine Humans Pharmacology (medical) Rheumatoid arthritis CXCL13 Migration B cell 030304 developmental biology B-Lymphocytes Regulatory [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system 0303 health sciences biology business.industry Interleukine-10 Chemokine CXCL13 Interleukin-10 Interleukin 10 medicine.anatomical_structure [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology biology.protein Cancer research Chemokines medicine.symptom business 030215 immunology Homing (hematopoietic) |
| Zdroj: | Rheumatology Rheumatology, 2021, 61 (5), pp.2185-2196. ⟨10.1093/rheumatology/keab639⟩ Rheumatology, Oxford University Press (OUP), 2021, ⟨10.1093/rheumatology/keab639⟩ |
| ISSN: | 1462-0332 1462-0324 1460-2172 |
| Popis: | Objectives Chemokines (CKs) are key players of immune-cell homing and differentiation. CK receptors (CKRs) can be used to define T-cell functional subsets. We aimed to characterize the CKR profile of the regulatory B-cell subset B10+ cells and investigate the CKs involved in their migration and differentiation in healthy donors and patients with RA. Methods RNA sequencing and cytometry were used to compare CKR expression between B10+ and B10neg cells. Migration of B10+ and B10neg cells and IL-10 secretion of B cells in response to recombinant CKs or synovial fluid (SF) were assessed. Results CXCR5 was expressed at a higher level on the B10+ cell surface as compared with other B cells (referred to as B10neg cells). In line with this, its ligand CXCL13 preferentially attracted B10+ cells over B10neg cells. Interestingly, synovial fluid from RA patients contained high levels of CXCL13 and induced strong and preferential migration of B10+ cells. Besides its role in attracting B10+ cells, CXCL13 also promoted IL-10 secretion by B cells. In RA patients, the level of CXCR5 on B-cell surface was reduced. The preferential migration of RA B10+ cells toward CXCL13-rich SF was lost and CXCL13 stimulation triggered less IL-10 secretion than in healthy donors. Conclusion Our results identify that the CXCR5/CXCL13 axis is essential for B10+ cell biology but is defective in RA. Restoring the preferential migration of B10+ within the affected joints to better control inflammation may be part of the therapeutic approach for RA. |
| Databáze: | OpenAIRE |
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