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Abstract：
Protein kinase C delta (PKCδ) has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCδ-deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement for PKCδ in preventing lupus autoimmunity, this critical tolerance mechanism remains poorly understood. We recently reported that PKCδ acts as a key regulator of B cell tolerance by selectively deleting anti-dsDNA B cells in the germinal center (GC). PKCδ\'s tolerance function is activated by sphingomyelin synthase 2 (SMS2), a lipid enzyme whose expression is generally reduced in B cells from lupus patients. Moreover, pharmacologic strengthening of the SMS2/PKCδ tolerance pathway alleviated lupus pathogenesis in mice. Here, we review relevant publications in order to provide mechanistic insights into PKCδ\'s tolerance activity and discuss the potential significance of therapeutically targeting PKCδ\'s tolerance activity in the GC for selectively inhibiting lupus autoimmunity.
摘要：
蛋白激酶Cδ（PKCδ）已成为系统性红斑狼疮（SLE或狼疮）的关键保护分子，一种以抗双链（ds）DNAIgG为特征的自身免疫性疾病。尽管PKCδ缺陷小鼠和PRKCD基因突变的狼疮患者清楚地证明了PKCδ在预防狼疮自身免疫中的需求，这种关键的耐受机制仍然知之甚少。我们最近报道，PKCδ通过选择性删除生发中心（GC）中的抗dsDNAB细胞而充当B细胞耐受性的关键调节剂。PKCδ的耐受功能被鞘磷脂合酶2（SMS2）激活，在狼疮患者的B细胞中表达通常降低的脂质酶。此外，SMS2/PKCδ耐受途径的药理学加强减轻了小鼠狼疮的发病机制。这里,我们回顾了相关出版物，以提供对PKCδ耐受活性的机制见解，并讨论在GC中治疗靶向PKCδ耐受活性对选择性抑制狼疮自身免疫的潜在意义。
