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

被引：0

作者：

Zhang, Jiali ^{[1
,2
,3
]}

Yuan, Ying ^{[1
,2
,3
]}

Ni, Shuangying ^{[1
,2
,3
]}

Mu, Siqi ^{[8
]}

Wang, Wanrong ^{[8
]}

Sun, Feiyang ^{[8
]}

Liang, Bo ^{[1
,2
,3
]}

Lu, Peng ^{[1
,2
,3
]}

Qiu, Yue ^{[1
,2
,3
]}

Du, Wenhui ^{[1
,2
,3
]}

Wang, Chenjun ^{[6
]}

Duan, Huijie ^{[6
]}

Hu, Zejuan ^{[6
]}

Wen, Leilei ^{[1
,2
,3
]}

Zheng, Xiaodong ^{[1
,2
,3
]}

Sheng, Yujun ^{[9
]}

Zhang, Shengquan ^{[7
]}

Chen, Shanyu ^{[5
]}

Yin, Xueli ^{[4
]}

Zhu, Zhengwei ^{[1
,2
,3
,6
]}

机构：

[1] Anhui Med Univ, Affiliated Hosp 1, Inst Dermatol, Hefei, Peoples R China

[2] Anhui Med Univ, Affiliated Hosp 1, Dept Dermatol, Hefei, Peoples R China

[3] Anhui Med Univ, Key Lab Dermatol, Minist Educ, Hefei, Peoples R China

[4] Anhui Med Univ, Funct Expt Ctr, Sch Basic Med Sci, Hefei, Peoples R China

[5] Anhui Med Univ, Affiliated Hosp 1, Dept Rheumatol & Immunol, Hefei, Peoples R China

[6] Shannan Peoples Hosp, Dept Dermatol, Shannan, Peoples R China

[7] Anhui Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hefei, Peoples R China

[8] Anhui Med Univ, Clin Med Coll 1, Hefei, Peoples R China

[9] Friendship Hosp, Dept Dermatol, Beijing, Peoples R China

来源：

CLINICAL RHEUMATOLOGY | 2025年 / 44卷 / 07期

基金：

中国国家自然科学基金;

关键词：

LncRNA PVT1; Systemic lupus erythematosus (SLE); CD4(+)T cells; MRL/lpr mice; MiRNA-30e-5p; LONG NONCODING RNAS; T-CELLS; DIFFERENTIATION; MECHANISMS; IMBALANCE; APOPTOSIS; RESPONSES; DYNAMICS;

D O I：

10.1007/s10067-025-07519-4

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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-beta) 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-beta 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/ROR gamma t/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.

引用

页码：2741 / 2750

页数：10

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