Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Int Immunopharmacol. 2024 Jan 5;126:111256. doi: 10.1016/j.intimp.2023.111256. Epub 2023 Nov 22.
The inflammatory response runs through the whole pathogenesis of systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSC) have exhibited a positive therapeutic effect on SLE. This study aimed to ascertain the pathogenic role of inflammasome activation in SLE and whether MSC alleviate SLE by suppressing it. The results showed that the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome was activated in macrophages from MRL/lpr mice and patients with SLE, correlating with disease activity. After MSC transplantation, the disease severity in MRL/lpr mice was alleviated, and NLRP3 inflammasome activation was inhibited with decreased levels of NLRP3 and caspase-1 in macrophages. Furthermore, lower serum levels of interleukin (IL)-1β and IL-18 were observed in patients with SLE who underwent MSC transplantation. In vitro and in vivo studies indicated that MSC suppressed NLRP3 inflammasome activation by inhibiting Pim-1 expression. The findings provide an updated view of inflammasome signaling in SLE. Additionally, MSC ameliorated SLE by inhibiting NLRP3 inflammasome activation, implying a possible molecular mechanism for the clinical application of MSC and a potential therapeutic target in patients with SLE.
炎症反应贯穿系统性红斑狼疮 (SLE) 的整个发病机制。间充质干细胞 (MSC) 对 SLE 表现出积极的治疗作用。本研究旨在确定炎症小体激活在 SLE 中的发病作用，以及 MSC 是否通过抑制其活性来缓解 SLE。结果表明，MRL/lpr 小鼠和 SLE 患者的巨噬细胞中核苷酸结合寡聚结构域样受体 3 (NLRP3) 炎症小体被激活，与疾病活动相关。MSC 移植后，MRL/lpr 小鼠的疾病严重程度得到缓解，巨噬细胞中 NLRP3 和半胱天冬酶-1 的水平降低，NLRP3 炎症小体的激活受到抑制。此外，接受 MSC 移植的 SLE 患者的血清白细胞介素 (IL)-1β 和 IL-18 水平降低。体外和体内研究表明，MSC 通过抑制 Pim-1 表达抑制 NLRP3 炎症小体激活。这些发现为 SLE 中的炎症小体信号提供了新的视角。此外，MSC 通过抑制 NLRP3 炎症小体激活改善 SLE，这表明 MSC 临床应用的可能分子机制和 SLE 患者的潜在治疗靶点。
