Systemic lupus erythematosus (SLE) is a complex autoimmune disease that exhibits a strong female bias (female-to-male ratio 9:1) in patients. Further, 40-60% SLE patients develop lupus nephritis (LN), which significantly increases the mortality rates. The failure of current therapies to adequately treat LN in patients reflects an incomplete understanding of the disease pathogenesis. Notably, a chronic increase in serum interferon-α (IFN-α) activity is a heritable risk factor to develop SLE. Accordingly, blood cells from most SLE patients with an active disease exhibit an increase in the expression of the type I IFN (IFN-α/β)-stimulated genes (ISGs, also referred to as "IFN-signature"), a type I IFN response. Further, LN patients during renal flares also exhibit an "IFN-signature" in renal biopsies. Therefore, an improved understanding of the regulation of type I IFNs expression is needed. Basal levels of the IFN-β through "priming" of IFN-α producing cells augment the expression of the IFN-α genes. Of interest, recent studies have indicated a role for the type I IFN-inducible Absent in Melanoma 2 proteins (the murine Aim2 and human AIM2) in the negative regulation of the type I IFN response through inflammasome-dependent and independent mechanisms. Further, an increase in the expression of Aim2 and AIM2 proteins in kidney and renal macrophages associated with the development of nephritis. Therefore, we discuss the role of Aim2/AIM2 proteins in the regulation of type I IFNs and LN. An improved understanding of the mechanisms by which the Absent in Melanoma 2 proteins suppress the type I IFN response and modulate nephritis is key to identify novel therapeutic targets to treat a group of LN patients.

中文翻译：

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干扰素 (IFN) 诱导型黑色素瘤 2 蛋白中缺乏 I 型 IFN 反应的负调节：对狼疮性肾炎的影响

系统性红斑狼疮 (SLE) 是一种复杂的自身免疫性疾病，患者表现出强烈的女性偏见（男女比例 9:1）。此外，40-60% 的 SLE 患者会发展为狼疮性肾炎 (LN)，这会显着增加死亡率。当前疗法未能充分治疗患者的 LN，反映了对疾病发病机制的不完全了解。值得注意的是，血清干扰素-α (IFN-α) 活性的慢性增加是发展为 SLE 的遗传风险因素。因此，来自大多数患有活动性疾病的 SLE 患者的血细胞表现出 I 型 IFN（IFN-α/β）刺激基因（ISG，也称为“IFN 特征”）的表达增加，这是一种 I 型干扰素反应。此外，肾病发作期间的 LN 患者在肾活检中也表现出“干扰素特征”。所以，需要更好地了解 I 型干扰素表达的调节。通过“引发”产生 IFN-α 的细胞，IFN-β 的基础水平增加了 IFN-α 基因的表达。有趣的是，最近的研究表明，黑色素瘤 2 蛋白（鼠类 Aim2 和人 AIM2）中 I 型 IFN 诱导的缺失在通过炎症小体依赖性和独立机制对 I 型 IFN 反应的负调节中发挥作用。此外，肾脏和肾脏巨噬细胞中 Aim2 和 AIM2 蛋白表达的增加与肾炎的发展有关。因此，我们讨论了 Aim2/AIM2 蛋白在 I 型干扰素和 LN 调节中的作用。