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Despite advances in understanding SLE pathogenesis, the molecular mechanisms driving aberrant B cell differentiation remain elusive. Melatonin, a neuroendocrine hormone with immunomodulatory properties, has been shown to regulate immune responses, but its role in B cell differentiation and SLE is poorly understood. This study investigates the role of melatonin and its receptors in B cell differentiation and SLE pathogenesis. We observed reduced serum melatonin levels and decreased expression of melatonin receptors in B cells from SLE patients and MRL\/Lpr mice. Activation of melatonin receptors inhibited the protein kinase A (PKA) signaling pathway and reduced phosphorylation of cyclic\u2010AMP response binding protein (CREB), leading to epigenetic downregulation of PRDM1 and IRF4, key transcription factors for plasmablast and plasma cell differentiation. Consequently, melatonin receptor activation suppressed abnormal B cell differentiation into antibody\u2010secreting cells. Our findings highlight melatonin and its receptor signaling as potential therapeutic targets for SLE and other autoimmune diseases mediated by aberrant antibody\u2010secreting cell activity. This study provides novel insights into the protective role of melatonin in SLE and offers a promising avenue for developing targeted therapies.<\/jats:p>","DOI":"10.1111\/jpi.70093","type":"journal-article","created":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T07:29:38Z","timestamp":1761463778000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melatonin Inhibits Antibody\u2010Secreting Cells and Improves Systemic Lupus Erythematosus via Modulation of the PKA\u2010CREB Signaling Pathway"],"prefix":"10.1111","volume":"77","author":[{"given":"Pei","family":"Du","sequence":"first","affiliation":[{"name":"Department of Dermatology, Human Key Laboratory of Medical Epigenomics, the Second Xiangya Hospital Central South University Changsha 410011 China"},{"name":"Department of Pathology, Xiangya Hospital Central South University Changsha 410008 Hunan 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