褪黑素
褪黑激素受体
信号转导
受体
下调和上调
免疫系统
生物
免疫学
内分泌学
自身抗体
红斑狼疮
癌症研究
B细胞
细胞分化
内科学
细胞
系统性红斑狼疮
蛋白激酶A
细胞生物学
激素
细胞信号
转录因子
自身免疫性疾病
激酶
细胞生长
B细胞受体
自身免疫
表观遗传学
细胞表面受体
化学
T细胞
作者
Pei Du,Yaqin Yu,Wenqian Zhang,Ke Sun,Wei He,Ming Zhao,Sujie Jia
摘要
Systemic lupus erythematosus (SLE) is an autoimmune disorder featuring abnormal B cell differentiation and excessive autoantibody production, leading to multiorgan damage. 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-AMP 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-secreting cells. Our findings highlight melatonin and its receptor signaling as potential therapeutic targets for SLE and other autoimmune diseases mediated by aberrant antibody-secreting cell activity. This study provides novel insights into the protective role of melatonin in SLE and offers a promising avenue for developing targeted therapies.
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