{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:53:36Z","timestamp":1793224416700,"version":"4.5.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is a complex autoimmune disorder driven by autoreactive B cells and characterized by the production of pathogenic autoantibodies. Belimumab, an anti-BAFF monoclonal antibody, has demonstrated efficacy in reducing disease activity and corticosteroid use in SLE patients, although responses remain variable. B-cell activating factor (BAFF) is essential for B cell survival and autoantibody production, positioning it as a key target in SLE pathogenesis. MicroRNAs (miRNAs), critical regulators of gene expression and immune homeostasis, have an emerging role in SLE pathophysiology. However, their regulation in response to anti-BAFF therapies, such as belimumab, remains unexplored. This study investigates miRNA-mRNA interactions in T cells, B cells, and myeloid cells from SLE patients before and after belimumab treatment. A total of 79 miRNAs associated with treatment response and 525 miRNA-gene interactions were identified. Validation in 18 SLE responders revealed significant changes in miRNA expression in T and myeloid cells, but not in B cells. Belimumab was found to modulate B cell development by regulating genes such as BLNK, BANK1, and MEF2C, as well as the CD40\/CD40L axis. In T cells, miRNAs influenced interferon signaling and inflammatory cytokines via NF-\u03baB activation. Changes in myeloid cells, characterized by the downregulation of KLF13, CCL5, and IL4, appear to be secondary to T cell modulation. These findings provide novel insights into the miRNA-mediated regulatory networks underlying belimumab\u2019s immunomodulatory effects in\u00a0SLE.\u00a0Further research is required to validate these findings and through <jats:italic>in\u00a0vitro<\/jats:italic>\u00a0experiments to better understand the role of miRNAs in guiding treatment responses.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1553971","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T07:08:32Z","timestamp":1741936112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrative miRNA-mRNA profiling uncovers mechanisms of belimumab action in systemic lupus 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