Department of Dermatology, Huashan Hospital, Shanghai Institute of Dermatology, Fudan University, Shanghai, 200040, China.
Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
J Transl Med. 2023 Sep 29;21(1):678. doi: 10.1186/s12967-023-04427-6.
Psoriasis is an inflammatory disease mediated by helper T (Th)17 and Th1 cells. MicroRNA-125a (miR-125a) is reduced in the lesional skin of psoriatic patients. However, the mechanism by which miR-125a participates in psoriasis remains unclear.
The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4 T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo.
miR-125a-5p was downregulated in peripheral blood CD4 T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4 T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells.
miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ.
银屑病是一种由辅助性 T（Th）17 和 Th1 细胞介导的炎症性疾病。在银屑病患者的皮损皮肤中，miR-125a（miR-125a）的水平降低。然而，miR-125a 参与银屑病的机制尚不清楚。
通过实时定量 PCR（qRT-PCR）检测健康对照者和银屑病患者 CD4 T 细胞中 miR-125a-5p 及其下游靶标（ETS-1、IFN-γ和 STAT3）的水平。体外，通过转染 miR-125a-5p 模拟物，利用流式细胞术分析 miR-125a-5p 对 Th17 细胞分化的影响。采用咪喹莫特（IMQ）诱导的小鼠模型，评估皮内注射 agomir-125a-5p 上调 miR-125a-5p 在体内的作用。
银屑病患者外周血 CD4 T 细胞中 miR-125a-5p 下调，与调节性 T 细胞（Tregs）的比例呈正相关，与银屑病面积和严重程度指数（PASI）评分呈负相关。此外，miR-125a-5p 模拟物促进 Tregs 的分化，并下调鼠 CD4 T 细胞中 ETS-1、IFN-γ和 STAT3 的信使 RNA（mRNA）水平。此外，agomir-125a-5p 通过下调 Th17 细胞的比例缓解了 IMQ 诱导的小鼠模型中的银屑病样炎症。
miR-125a-5p 可能通过靶向 STAT3 恢复 Tregs 对 Th17 细胞的抑制功能，通过靶向 ETS-1 和 IFN-γ 间接恢复 Tregs 对 Th1 细胞的抑制功能，从而在银屑病中具有治疗潜力。
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