Department of Dermatology, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China.
Department of Endocrinology, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China.
Mol Med Rep. 2021 Jan;23(1). doi: 10.3892/mmr.2020.11689. Epub 2020 Nov 17.
Vitiligo (VIT) is caused by loss and degradation of functional epidermal melanocytes. Studies have indicated that melanocyte destruction may be associated with an imbalance between regulatory T cells (Treg cells) and effector T cells (Teff cells). The current study aimed to investigate the molecular mechanism through which Treg/Teff balance affects VIT pathogenesis. To explore this, peripheral blood mononuclear cells were isolated from patients with VIT and healthy individuals. The present study revealed that the proportions of CD4 T cells, Treg cells and T helper 1 (Th1) cells were decreased in patients with VIT, but those of Teff cells (Th17 and Th22 cells) were increased; additionally, Foxp3 expression was decreased, but the expression levels of interferon‑γ, interleukin (IL)‑17A and IL‑22 were increased. Furthermore, in patients with VIT, microRNA (miR)‑21‑5p expression was decreased, while that of STAT3 was increased. Further in vitro experiments in CD4 T cells revealed that STAT3 was targeted by miR‑21‑5p. Functional analysis further indicated that miR‑21‑5p overexpression in Th17‑polarized CD4 T cells decreased the proportion of Teff cells and associated cytokines, such as IL‑17A and IL‑22, but increased the proportion of Treg cells and Foxp3. However, the effects of miR‑21‑5p overexpression were partly reversed by STAT3 overexpression. Increased apoptosis of melanocytes was detected after co‑culture with Th17‑polarized CD4 T cells in the presence of a miR‑21‑5p mimic. However, this indirect effect of the miR‑21‑5p mimic on melanocytes was decreased via STAT3 overexpression. Therefore, miR‑21‑5p may protect melanocytes via targeting STAT3 and regulating Treg/Teff balance. The current findings may provide a possible treatment method for managing VIT.
白癜风（VIT）是由功能性表皮黑素细胞的丧失和降解引起的。研究表明，黑素细胞破坏可能与调节性 T 细胞（Treg 细胞）和效应 T 细胞（Teff 细胞）之间的失衡有关。本研究旨在探讨 Treg/Teff 平衡影响 VIT 发病机制的分子机制。为了探索这一点，从 VIT 患者和健康个体中分离外周血单核细胞。本研究表明，VIT 患者的 CD4 T 细胞、Treg 细胞和辅助性 T 细胞 1（Th1）细胞比例降低，但 Teff 细胞（Th17 和 Th22 细胞）比例升高；此外，Foxp3 表达降低，而干扰素-γ、白细胞介素（IL）-17A 和 IL-22 的表达水平升高。此外，在 VIT 患者中，微小 RNA（miR）-21-5p 的表达降低，而 STAT3 的表达增加。进一步的体外实验在 CD4 T 细胞中表明，STAT3 是 miR-21-5p 的靶点。功能分析进一步表明，Th17 极化的 CD4 T 细胞中 miR-21-5p 的过表达降低了 Teff 细胞及其相关细胞因子（如 IL-17A 和 IL-22）的比例，但增加了 Treg 细胞和 Foxp3 的比例。然而，miR-21-5p 过表达的作用部分被 STAT3 过表达逆转。在 miR-21-5p 模拟物存在下与 Th17 极化的 CD4 T 细胞共培养后，检测到黑素细胞凋亡增加。然而，miR-21-5p 模拟物对黑素细胞的这种间接作用通过 STAT3 过表达而降低。因此，miR-21-5p 通过靶向 STAT3 并调节 Treg/Teff 平衡来保护黑素细胞。目前的研究结果可能为管理 VIT 提供一种可能的治疗方法。
