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register hereAn important pathogenic role for neutrophils in systemic lupus erythematosus (SLE) has been proposed. Neutrophils that lack brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1), one of the clock genes, are defective in aging and proinflammatory responses.

在此登记已经提出了中性粒细胞在系统性红斑狼疮（SLE）中的重要致病作用。缺乏大脑和肌肉芳烃受体核转运体样1（Bmal1）（时钟基因之一）的中性粒细胞在衰老和促炎反应方面存在缺陷。

We assessed the role of Bmal1 in clinical and immunologic manifestations of murine lupus and in human SLE neutrophils.Myeloid-conditional Bmal1 knockout mice (Bmal1 Mye-/-) and wild type (WT) were treated with epicutaneous TLR7/8 agonist (imiquimod; IMQ) for 6 weeks to induce a lupus phenotype. Upon euthanasia, immune responses, autoantibodies and renal manifestations were evaluated.

我们评估了Bmal1在小鼠狼疮和人类SLE中性粒细胞的临床和免疫学表现中的作用。用表皮TLR7/8激动剂（咪喹莫特；IMQ）处理骨髓条件性Bmal1敲除小鼠（Bmal1-Mye-/-）和野生型（WT）6周以诱导狼疮表型。安乐死后，评估免疫反应，自身抗体和肾脏表现。

NET formation and gene expression of bone marrow (BM)-derived murine neutrophils were evaluated. BMAL1 expression was quantified in SLE neutrophils and compared with clinical disease.Mye-/-and WT displayed comparable systemic inflammation. While renal function did not differ, serum anti-dsDNA levels and renal immune complex deposition were significantly increased in Bmal1 Mye-/-.

评估了骨髓（BM）衍生的小鼠嗜中性粒细胞的NET形成和基因表达。在SLE嗜中性粒细胞中定量BMAL1表达，并与临床疾病进行比较。Mye-/-和WT表现出相当的全身炎症。虽然肾功能没有差异，但Bmal1-Mye-/-的血清抗dsDNA水平和肾脏免疫复合物沉积显着增加。

While no differences were observed in NET formation, expression levels of April in BM neutrophils were significantly higher in Bmal1 Mye-/-. Bulk RNAsequence data showed that BM neutrophils in IMQ-treated Bmal1 Mye-/-were relatively immature when compared to IMQ-treated WT. BM showed enhanced April protein expression in Bmal1 Mye-/- mice.

虽然在NET形成中没有观察到差异，但Bmal1 Mye-/-中BM中性粒细胞中April的表达水平显着更高。大量RNA序列数据显示，与IMQ处理的WT相比，IMQ处理的Bmal1-Mye-/-中的BM中性粒细胞相对不成熟。BM在Bmal1-Mye-/-小鼠中显示出增强的April蛋白表达。

BMAL1 levels in human SLE peripheral blood neutrophils correlated positively with serum C3 and negatively with serum anti-dsDNA levels.Bmal1 is associated with lower disease activity in SLE. These results indicate that perturbation in the circadian rhythm of neutrophils can have pathogenic consequences in SLE..

人SLE外周血中性粒细胞中的BMAL1水平与血清C3呈正相关，与血清抗dsDNA水平呈负相关。Bmal1与SLE中较低的疾病活动相关。这些结果表明，中性粒细胞昼夜节律的扰动可能在SLE中产生致病性后果。。