CXCR5/CXCL13 pathway, a key driver for migration of regulatory B10 cells, is defective in patients with rheumatoid arthritis
© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissionsoup.com..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:61 |
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| Enthalten in: |
Rheumatology (Oxford, England) - 61(2022), 5 vom: 05. Mai, Seite 2185-2196 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rempenault, Claire [VerfasserIn] |
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| Links: |
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| Themen: |
130068-27-8 |
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| Anmerkungen: |
Date Completed 09.05.2022 Date Revised 31.05.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/rheumatology/keab639 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM329259466 |
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| 100 | 1 | |a Rempenault, Claire |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CXCR5/CXCL13 pathway, a key driver for migration of regulatory B10 cells, is defective in patients with rheumatoid arthritis |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IL-10 | |
| 650 | 4 | |a RA | |
| 650 | 4 | |a Regulatory B cells | |
| 650 | 4 | |a chemokines | |
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| 650 | 4 | |a migration | |
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| 700 | 1 | |a Mielle, Julie |e verfasserin |4 aut | |
| 700 | 1 | |a Schreiber, Kristina |e verfasserin |4 aut | |
| 700 | 1 | |a Corbeau, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Macia, Laurence |e verfasserin |4 aut | |
| 700 | 1 | |a Combe, Bernard |e verfasserin |4 aut | |
| 700 | 1 | |a Morel, Jacques |e verfasserin |4 aut | |
| 700 | 1 | |a Daien, Claire Immediato |e verfasserin |4 aut | |
| 700 | 1 | |a Audo, Rachel |e verfasserin |4 aut | |
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