Abstract：
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.
摘要：
炎症反应贯穿于系统性红斑狼疮(SLE)的整个发病机制。间充质干细胞（MSC）对SLE具有积极的治疗作用。本研究旨在确定炎症小体激活在SLE中的致病作用以及MSC是否通过抑制它来缓解SLE。结果表明，在MRL/lpr小鼠和SLE患者的巨噬细胞中，核苷酸结合寡聚化结构域样受体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，NLRP3炎性小体的激活随着巨噬细胞中NLRP3和caspase-1水平的降低而受到抑制。此外，在接受MSC移植的SLE患者中观察到较低的血清白细胞介素（IL）-1β和IL-18水平。体外和体内研究表明，MSC通过抑制Pim-1表达来抑制NLRP3炎性体的活化。这些发现提供了SLE中炎症小体信号的最新观点。此外,MSC通过抑制NLRP3炎性体激活改善SLE，提示MSC的临床应用可能的分子机制和SLE患者的潜在治疗靶标。
