Armas-González, Estefanía Domínguez-Luis, María Jesús Díaz-Martín, Ana Arce-Franco, Mayte Castro-Hernández, Javier Danelon, Gabriela Hernández-Hernández, Vanesa Bustabad-Reyes, Sagrario Cantabrana, Alberto Uguccioni Díaz-González, Federico 2018-06-07 Background: B cells exert their pathogenic action in rheumatoid arthritis (RA) locally in the synovium. This study was undertaken to elucidate the chemokines responsible for the recruitment of B cells in the inflamed synovium, taking into account that the rich chemokine milieu present in the synovial tissue can fine-tune modulate discrete chemokine receptors. Methods: Expression levels of chemokine receptors from the CC and CXC family, as well as CD27, were assessed by flow cytometry in CD20+ mononuclear cells isolated from the peripheral blood (PB) and synovial fluid (SF) of RA and psoriatic arthritis patients. Transwell experiments were used to study migration of B cells in response to a chemokine or in the presence of multiple chemokines. Results: B cells from the SF of arthritis patients showed a significant increase in the surface expression of CCR1, CCR2, CCR4, CCR5 and CXCR4 with respect to PB. Conversely, SF B cells expressed consistently lower amounts of CXCR5, CXCR7 and CCR6, independent of CD27 expression. Analysis of permeabilized B cells suggested internalization of CXCR5 and CCR6 in SF B cells. In Transwell experiments, CCL20 and CXCL13, ligands of CCR6 and CXCR5, respectively, caused a significantly higher migration of B cells from PB than of those from SF of RA patients. Together, these two chemokines synergistically increased B-cell migration from PB, but not from SF. Conclusions: These results suggest that CXCL13 and CCL20 might play major roles in RA pathogenesis by acting singly on their selective receptors and synergistically in the accumulation of B cells within the inflamed synovium. application/pdf https://n2t.net/ark:/12658/srd1318905 https://susi.usi.ch/global/documents/318905 https://susi.usi.ch/documents/318905/files/Armas-Gonzalez_ART_2018.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1186/s13075-018-1611-2 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318905 info:eu-repo/semantics/openAccess CC BY Arthritis research & therapy. - 2018, vol. 20, p. 114 Rheumatoid arthritis Psoriatic arthritis B cells Chemokines and chemokine receptors info:eu-repo/classification/udc/61 Role of CXCL13 and CCL20 in the recruitment of B cells to inflammatory foci in chronic arthritis http://purl.org/coar/resource_type/c_6501