机构：[1]Department of Disease Control and Prevention, The First People’s Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China云南省第一人民医院[2]Department of Rheumatology, The First People’s Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China内科片风湿免疫科云南省第一人民医院[3]School of Public Health, Dali University, Dali, Yunnan 671013, China[4]Department of Laboratory Medicine, The First People’s Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China医技片检验科云南省第一人民医院[5]Department of Nephrology, The First People’s Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China内科片肾内科云南省第一人民医院
Purpose: This study aimed to explore the mechanism by which systemic lupus erythematosus (SLE) activity is promoted through Treg inhibition from the perspective of ceRNA. Methods: qRT-PCR was used to detect the expressions of circETS1, miR-1205, and FoxP3 in clinical SLE patient samples. Overexpression of circETS1and miR-1205, along with knockdown of miR-1205 and FoxP3 were conducted in CD4+ T cells, while the proliferation of helper T cell 17 (Th17) and regulatory T cell (Treg) was detected. Arescue assay was performed to verify the molecular mechanism of circETS1/miR-1205/Foxp3 mRNA axis in regulating CD4+ T cell differentiation. In the in vivo experiment, the expression of miR-1205 in SLE mice was intervened, and renal function, inflammatory factors, and serum complement were measured. Additionally, Treg/Th17 cell ratio was detected by flow cytometry. Results: In SLE patients, Treg cells were found to decrease, while Th17 cells increased. Transfection with circETS1 overexpression led to CD4+ T cells differentiating into Treg cells, causing an imbalance in the Th17/Treg ratio. Transfection of miR-1205 mimic and si-FoxP3 could reverse the effect of circETS1 overexpression. Moreover, inhibiting the expression of miR-1205 showed therapeutic effects on SLE mice. Conclusion: circETS1 inhibits Treg via the miR-1205/FoxP3 axis, thereby promoting SLE activity, which may become a new target for SLE treatment.
基金：
National Natural Science Foundation of China [82060305]; Yunnan Province Applied Basic Research/Kunming Medical University Joint Special Project [202301AY070001-069]
第一作者机构：[1]Department of Disease Control and Prevention, The First People’s Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Disease Control and Prevention, The First People’s Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650034, China[*1]Department of Disease Control and Prevention, The First People’s Hospital of Yunnan Province The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Xishan District, Kunming, Yunnan Province 650034, China
推荐引用方式(GB/T 7714)：
Zou Hongju,Ma Sha,Li Li,et al.Downregulation of circular RNA ETS1 promotes SLE activity and inhibits Treg cell differentiation through miR-1205/FoxP3 molecular axis[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2024,128:doi:10.1016/j.intimp.2024.111539.
APA：
Zou, Hongju,Ma, Sha,Li, Li,Xia, Xixi,Zhou, Yan&Zhang, Ruixian.(2024).Downregulation of circular RNA ETS1 promotes SLE activity and inhibits Treg cell differentiation through miR-1205/FoxP3 molecular axis.INTERNATIONAL IMMUNOPHARMACOLOGY,128,
MLA：
Zou, Hongju,et al."Downregulation of circular RNA ETS1 promotes SLE activity and inhibits Treg cell differentiation through miR-1205/FoxP3 molecular axis".INTERNATIONAL IMMUNOPHARMACOLOGY 128.(2024)
医学