ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/001/SRR13088301/SRR13088301.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/099/SRR13088299/SRR13088299.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/095/SRR13088295/SRR13088295.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/096/SRR13088296/SRR13088296.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/097/SRR13088297/SRR13088297.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/002/SRR13088302/SRR13088302.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/098/SRR13088298/SRR13088298.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/094/SRR13088294/SRR13088294.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/000/SRR13088300/SRR13088300.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/091/SRR13088291/SRR13088291.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/092/SRR13088292/SRR13088292.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/093/SRR13088293/SRR13088293.fastq.gzprimary200OKGenomicsKyushu Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA679601Homo sapiensObjective: T follicular regulatory (Tfr) cells express CXC chemokine receptor type 5. They migrate into germinal centers and suppress T follicular helper (Tfh) and B cells for regulating antibody production. Tumor necrosis factor (TNF) inhibitors are used in inflammatory diseases however, autoantibody and anti-drug antibody production is challenging. As TNF receptor 2 (TNFR2) signaling is important for suppressive functions of regulatory T cells, we investigated the role of TNFR2 on Tfr cells. Methods: Tfr, Tfh, and naive B cells were obtained from human peripheral blood. Tfr cells were stimulated with MR2-1 (anti-TNFR2 agonistic antibody) and their proliferation, Forkhead box P3 (Foxp3) expression, and surface molecules were evaluated by flow cytometry. Tfh/B-cell proliferation and B-cell IgM production and differentiation in co-cultures with MR2-1-stimulated Tfr cells were examined. Results: TNFR2 expression was higher on Tfr cells than conventional T cells. MR2-1 altered the gene expression profile of Tfr cells. Cell proliferation and Foxp3 expression were induced by MR2-1. Inducible costimulator and program death-1 were dramatically upregulated in MR2-1-stimulated Tfr cells and significantly suppressed Tfh/B-cell proliferation, IgM production, and B-cell differentiation. Tfr cells treated with MR2-1 migrated according to the CXCL13 gradient. Conclusion: TNFR2 signaling in Tfr cells regulates Tfh and B-cell population. Aberrant antibody production during TNF inhibitor treatment might be associated with TNFR2 signaling inhibition in Tfr cells, suggesting TNFR1-specific inhibition as a better therapeutic strategy than pan-TNF inhibition. TNFR2-treated Tfr cells may serve as prospective candidates for cell-based therapy of autoimmune diseases. Overall design: Transcriptome analysis of Tfr cells and Treg cells with or without TNFR2 stimulation.ENAdif, tnfa, TNF-alpha, human being, Man (Taxonomy), regg1, xtnf, TNF, RATTNF, CG12919, Modern, Aptitudes, TNFA, ggr, Talents, TNFalpha, BcDNA:RH51659, DmelCG12919, Ect1, human, DIF, dt1, Ability, Human, tnfsf2, Abilities, TNF-a, darth, signalling process, Homo sapiens, Talent, Regg1, Modern Man, tnf-alpha, TNFSF2, Egr, Tnfa, Cell., xtnf-alpha, Man, Tnfsf1a, humans, single organism signalingdif, tnfa, TNF-alpha, human being, Man (Taxonomy), regg1, xtnf, TNF, RATTNF, CG12919, Modern, Aptitudes, TNFA, ggr, Talents, TNFalpha, BcDNA:RH51659, DmelCG12919, Ect1, human, DIF, dt1, Ability, Human, tnfsf2, Abilities, TNF-a, darth, signalling process, Homo sapiens, Talent, Regg1, Modern Man, tnf-alpha, TNFSF2, Egr, Tnfa, Cell., xtnf-alpha, Man, Tnfsf1a, humans, single organism signalingfalseTNF-receptor 2 signaling enhances suppressive abilities in human circulating T follicular regulatory cellsTNF-receptor 2 signaling enhances suppressive abilities in human circulating T follicular regulatory cells2025-09-242021-12-23PRJNA679601GSE1618359606