Xu Min, Li Xiaoliu, Bao Cheng, Zhang Yue, Yang Jinghan, Hang Yang, Sun Lingyun, Chen Hongwei
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, 210008, China.
Department of Rheumatology and Immunology, Joint Institute of Nanjing Drum Tower Hospital for Life and Health, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu Province, 210008, China.
Cell Immunol. 2025 Aug;414:104996. doi: 10.1016/j.cellimm.2025.104996. Epub 2025 Jun 16.
Curcumin extracted from the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antitumour properties. In previous studies, curcumin has been reported to have therapeutic effects on systemic lupus erythematosus (SLE), in which the upregulation of double-negative T (DNT) cells was detected. Therefore, the purpose of this study is to explore the role of curcumin in the remission of SLE by regulating DNT cell homeostasis.
Two established murine models of lupus, MRL/lpr mice and R848-induced mice, were administered with 50 mg/kg curcumin to evaluate its therapeutic effects. Flow cytometry was used to detect the proportions of DNT cells, Treg cells and Th cells in mouse tissues. H&E staining and immunofluorescence were used to assess inflammatory cell infiltration and immune complex deposition in the kidney. Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were used to detect the expression of inflammatory factors. RNA sequencing was used to identify differentially expressed genes and explore regulatory mechanisms, and western blot was used to detect protein expression.
Our results suggest that the accumulation of DNT cells is closely associated with lupus pathogenesis and development in both mouse models, whereas curcumin treatment can improve lupus serological and immunological profiles, and regulate T-cell homeostasis, especially DNT cells. Further studies demonstrated that curcumin promoted DNT cell apoptosis to eventually decrease the accumulation of DNT cells.
Curcumin can improve lupus serological and immunological profiles as well as renal pathology by suppressing DNT cells, and may be a potential candidate for the treatment of SLE.
从姜黄根茎中提取的姜黄素具有抗炎、抗氧化和抗肿瘤特性。在先前的研究中，已报道姜黄素对系统性红斑狼疮（SLE）具有治疗作用，其中检测到双阴性T（DNT）细胞上调。因此，本研究的目的是探讨姜黄素通过调节DNT细胞稳态在SLE缓解中的作用。
给两种已建立的狼疮小鼠模型，即MRL/lpr小鼠和R848诱导的小鼠，给予50mg/kg姜黄素以评估其治疗效果。流式细胞术用于检测小鼠组织中DNT细胞、调节性T细胞（Treg细胞）和辅助性T细胞（Th细胞）的比例。苏木精-伊红（H&E）染色和免疫荧光用于评估肾脏中的炎性细胞浸润和免疫复合物沉积。酶联免疫吸附测定（ELISA）和实时定量聚合酶链反应（RT-qPCR）用于检测炎性因子的表达。RNA测序用于鉴定差异表达基因并探索调控机制，蛋白质印迹法用于检测蛋白质表达。
我们的结果表明，在两种小鼠模型中，DNT细胞的积累都与狼疮的发病机制和发展密切相关，而姜黄素治疗可改善狼疮的血清学和免疫学特征，并调节T细胞稳态，尤其是DNT细胞。进一步研究表明，姜黄素促进DNT细胞凋亡，最终减少DNT细胞的积累。
姜黄素可通过抑制DNT细胞改善狼疮的血清学和免疫学特征以及肾脏病理，可能是治疗SLE的潜在候选药物。
