LncRNA PVT1 regulates CD4 + T cell dysregulation in systemic lupus erythematosus: insights from human patients and MRL/lpr mouse.

OBJECTIVES

To investigate the role of lncRNA PVT1 in modulating CD4+ T cell subsets and its contribution to systemic lupus erythematosus (SLE) pathogenesis in human patients and MRL/lpr mice.

METHODS

Measured PVT1 and miR-30e-5p expression in SLE patients (n = 65) and healthy controls (HCs) using qRT-PCR. Analyzed Th1/Th2/Th17/Treg cell frequencies by flow cytometry and cytokine levels (IL-2, IL-4, IL-6, IL-17, TGF-β) via ELISA. Constructed lentiviral vectors to silence (SLE + si-Pvt1) or overexpress Pvt1 (SLE + lenti-Pvt1) in MRL/lpr mice (n = 40).

RESULTS

PVT1 was upregulated (p = 0.0488) and miR-30e-5p downregulated (p = 0.0095) in SLE patients. Th2 (p = 0.0165) and Th17 (p = 0.0017) cells exhibited a significant increase, while Th1 and Treg cells decreased. Pvt1 silencing reversed SLE phenotypes, increasing Th1 and Treg cells, reducing Th2 and Th17 cells, restoring IL-2 and TGF-β levels and reducing levels of IL-6 and IL-17. Overexpression of Pvt1 exacerbated disease severity. Pvt1 acted as a ceRNA to sponge miR-30e-5p, modulating T-bet/GATA3/RORγt/Foxp3 expression.

CONCLUSIONS

PVT1 dysregulation disrupts CD4+ T cell homeostasis in SLE. Targeting the PVT1/miR-30e-5p axis may restore immune balance and represent a novel therapeutic strategy. Key Points • Our data confirm the imbalance of CD4+ T cell subsets in SLE patients and demonstrate specific upregulation of lncRNA PVT1 expression in female SLE patients. • Targeting lncRNA PVT1 affects Th1/Th2 and Th17/Treg homeostasis in MRL/lpr mice. • Offers fresh insight into the dysregulation of lymphocyte subsets in SLE.