Mesenchymal stem cells attenuate systemic lupus erythematosus by inhibiting NLRP3 inflammasome activation through Pim-1 kinase

被引：6

作者：

Yu, Honghong ^{[1
]}

Li, Qi ^{[2
]}

Zhu, Huimin ^{[3
]}

Liu, Chang ^{[4
]}

Chen, Weiwei ^{[1
,5
]}

Sun, Lingyun ^{[1
,5
]}

机构：

[1] Nanjing Med Univ, Dept Rheumatol & Immunol, Nanjing Drum Tower Hosp, Clin Coll, Nanjing, Peoples R China

[2] Nanjing Univ Chinese Med, Clin Coll Tradit Chinese & Western Med, Nanjing Drum Tower Hosp, Dept Rheumatol & Immunol, Nanjing, Peoples R China

[3] Nanjing Univ, Nanjing Drum Tower Hosp, Dept Rheumatol & Immunol, Affiliated Hosp,Med Sch, Nanjing, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Nanjing Drum Tower Hosp, Grad Sch,Peking Union Med Coll, Dept Rhumatol & Immunol, Nanjing, Peoples R China

[5] Nanjing Med Univ, Drum Tower Clin Med Coll, 321 Zhongshan Rd, Nanjing 210008, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2024年 / 126卷

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

Mesenchymal stem cells; Systemic lupus erythematosus; NLRP3; Pim-1; EXPRESSION; MECHANISM; NEPHRITIS; AUTOPHAGY;

D O I：

10.1016/j.intimp.2023.111256

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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)-1 beta 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.

引用

页数：8