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.
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| http://dx.doi.org/10.1016/j.intimp.2024.111539 | DOI Listing |
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