Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China.
J Immunol Res. 2023 Aug 31;2023:7625817. doi: 10.1155/2023/7625817. eCollection 2023.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Approximately one-third to two-thirds of the patients with SLE progress to lupus nephritis (LN). The pathogenesis of SLE and LN has not yet been fully elucidated, and effective treatment for both conditions is lacking. The endoplasmic reticulum (ER) is the largest intracellular organelle and is a site of protein synthesis, lipid metabolism, and calcium storage. Under stress, the function of ER is disrupted, and the accumulation of unfolded or misfolded proteins occurs in ER, resulting in an ER stress (ERS) response. ERS is involved in the dysfunction of B cells, macrophages, T cells, dendritic cells, neutrophils, and other immune cells, causing immune system disorders, such as SLE. In addition, ERS is also involved in renal resident cell injury and contributes to the progression of LN. The molecular chaperones, autophagy, and proteasome degradation pathways inhibit ERS and restore ER homeostasis to improve the dysfunction of immune cells and renal resident cell injury. This may be a therapeutic strategy for SLE and LN. In this review, we summarize advances in this field.
系统性红斑狼疮（SLE）是一种复杂的自身免疫性疾病。大约三分之一至三分之二的 SLE 患者会进展为狼疮肾炎（LN）。SLE 和 LN 的发病机制尚未完全阐明，两种疾病都缺乏有效的治疗方法。内质网（ER）是最大的细胞内细胞器，是蛋白质合成、脂质代谢和钙储存的场所。在应激下，ER 的功能被打乱，未折叠或错误折叠的蛋白质在 ER 中积累，导致 ER 应激（ERS）反应。ERS 参与 B 细胞、巨噬细胞、T 细胞、树突状细胞、中性粒细胞等免疫细胞的功能障碍，导致免疫系统紊乱，如 SLE。此外，ERS 还参与肾固有细胞损伤，有助于 LN 的进展。分子伴侣、自噬和蛋白酶体降解途径抑制 ERS 并恢复 ER 稳态，以改善免疫细胞和肾固有细胞损伤的功能障碍。这可能是 SLE 和 LN 的一种治疗策略。在这篇综述中，我们总结了这一领域的进展。
