1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      CXCR5/CXCL13 pathway, a key driver for migration of regulatory B10 cells, is defective in patients with rheumatoid arthritis

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

          The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients.

            The immunosuppressive function of regulatory B cells has been shown in several murine models of chronic inflammation, including collagen-induced arthritis, inflammatory bowel disease, and experimental autoimmune encephalomyelitis. Despite interest in these cells, their relevance to the maintenance of peripheral tolerance in humans remains elusive. Here, we demonstrate that human CD19(+)CD24(hi)CD38(hi) B cells possessed regulatory capacity. After CD40 stimulation, CD19(+)CD24(hi)CD38(hi) B cells suppressed the differentiation of T helper 1 cells, partially via the provision of interleukin-10 (IL-10), but not transforming growth factor-beta (TGF-beta), and their suppressive capacity was reversed by the addition of CD80 and CD86 mAbs. In addition, CD19(+)CD24(hi)CD38(hi) SLE B cells isolated from the peripheral blood of systemic lupus erythematosus (SLE) patients were refractory to further CD40 stimulation, produced less IL-10, and lacked the suppressive capacity of their healthy counterparts. Altered cellular function within this compartment may impact effector immune responses in SLE and other autoimmune disorders. Copyright 2010 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found

              Human regulatory B cells in health and disease: therapeutic potential

              Regulatory B cells (Bregs) modulate immune responses predominantly, although not exclusively, via the release of IL-10. The importance of human Bregs in the maintenance of immune homeostasis comes from a variety of immune-related pathologies, such as autoimmune diseases, cancers, and chronic infections that are often associated with abnormalities in Breg numbers or function. A continuous effort toward understanding Breg biology in healthy individuals will provide new opportunities to develop Breg immunotherapy that could prove beneficial in treating various immune-mediated pathologies. In this Review, we discuss findings regarding human Bregs, including their mechanisms of suppression and role in different disease settings. We also propose several therapeutic strategies targeting Bregs for better management of immune disorders.
                Bookmark

                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Rheumatology
                Oxford University Press (OUP)
                1462-0324
                1462-0332
                May 01 2022
                May 05 2022
                August 11 2021
                May 01 2022
                May 05 2022
                August 11 2021
                : 61
                : 5
                : 2185-2196
                Affiliations
                [1 ]Rheumatology, CHU and University of Montpellier
                [2 ]IGMM, University of Montpellier, CNRS, Montpellier
                [3 ]Immunology, CHU and University of Montpellier, Nîmes
                [4 ]IGH, CNRS, Montpellier, France
                [5 ]Charles Perkins Centre, The University of Sydney, Sydney, Australia
                Article
                10.1093/rheumatology/keab639
                34382069
                aec2087d-4ed6-495d-9dc9-39e6994a2e16
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

                History

                Comments

                Comment on this article