Mature antigen‐experienced T helper cells synthesize and secrete the B cell chemoattractant CXCL13 in the inflammatory environment of the rheumatoid joint

Abstract

Objective. Synovial B cells play a critical role in rheumatoid arthritis (RA), being involved in autoantibody synthesis, T cell activation, and cytokine production. CXCL13 is a B cell chemoattractant that is instrumental in synovial B cell organization; the regulatory determinants of CXCL13 in inflammation are poorly characterized. This study was undertaken to investigate the functional involvement of synovial T cells in the ectopic expression of CXCL13 in RA.Methods. CXCL13 production and regulation were addressed using immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, multicolor flow cytometry, and enzyme-linked immunosorbent assay, by in situ-ex vivo analysis and in vitro functional assays with rheumatoid synovial tissue and primary cells. The recruitment and organization of B cells in the synovium are common events in rheumatoid arthritis (RA) and are thought to play a critical role in disease pathogenesis (1,2), by promoting autoantibody production (3) and the expression of proinflammatory cytokines through interaction with resident T cells (4). CXCL13 is a homeostatic B cell chemoattractant (5) that is required for the normal organization of B cell follicles in several secondary lymphoid organs (6) and is sufficient to promote B cell recruitment and ectopic Dr.

TNF-α promotes LPA1- and LPA3-mediated recruitment of leukocytes in vivo through CXCR2 ligand chemokines

“…CXCL13 is a homeostatic B cell chemoattractant ( 43 ) that is required for the normal organization of B cell follicles in secondary lymphoid organs ( 44 ) and for recruiting B cells in extralymphoid sites when overexpressed ( 45 ). CXCL13 mRNA and protein expression and spontaneous CXCL13 secretion were detected in RA synovial fl uid T cells ( 46 ), and it was suggested that CXCL13 tissue expression may be critically involved in the process of ectopic lymphoid neogenesis, a phenomenon seen in 25-50% of RA patients, via recruitment of B cells into the synovium ( 47 ). TREM-1 is an immunoglobulinlike cell surface receptor mainly expressed on neutrophils and CD14 monocytes ( 48 ).…”

CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer

“…CXCR5 -CXCL13 + CD4 + T cells have also been detected in rheumatoid synovitis from patients but were not viewed as T FH cells because of their CXCR5 negativity (26,27).…”

Exercise prevents the effects of experimental arthritis on the metabolism and function of immune cells

“…14,15 It is also important that the effects of exercise are verified on immune cells involved in the pathophysiology of RA, for example in LY and macrophages (MF). 16 18 Thus, the effects of exercise on the function of these cells can be investigated through the quantification of their glucose and glutamine metabolism.…”