Wei Yujia, Zhou Ting, Pan Ronghua, Nie Xiaoqi, Liu Zhong, Shi Zeqi, Zeng Ying, Zhang Ri, Deng Yunhua, Li Dong
Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Dermatol Sci. 2024 Feb;113(2):42-50. doi: 10.1016/j.jdermsci.2023.12.006. Epub 2023 Dec 24.
Plasma exosomal microRNAs (miRNAs) have been used as potential biomarkers for various diseases and have been investigated for their possible involvement in the pathogenesis of vitiligo. However, the miRNA expression profile of plasma exosomes in patients with non-segmental vitiligo (NSV) has not been determined yet.
To screen differentially expressed microRNAs in plasma exosomes derived from patients with NSV and explore their roles in the pathogenesis of NSV.
High-throughput sequencing was performed to determine the expression profiles of exosomal miRNAs in NSV. The effect of upregulated miR-1469 in NSV circulating exosomes on natural killer (NK) cells was further investigated using various molecular biological techniques.
MiR-1469 was identified as a candidate biomarker whose expression was significantly increased in circulating exosomes of NSV patients. Circulating exosomes were internalized by NK cells and increased NK cell proliferation viability and IFN-γ secretion capacity delivering miR-1469. Further studies revealed that the upregulation of CD122, the predicted target of miR-1469, could partially reverse the effect of miR-1469 on natural killer cells.
Alterations in plasma exosomal cargo occur in NSV and appear to contribute to NK cell dysfunction. Exosomal miR-1469 may be a biomarker of disease activity and could be used as a therapeutic drug target against innate immunity in NSV patients. The present study provides new insights into the role of exosomal miRNAs in NSV and suggests a novel miR-1469-CD122-IFN-γ pathway of NK cell underlying pathogenesis of NSV.
血浆外泌体微小RNA（miRNA）已被用作多种疾病的潜在生物标志物，并已对其可能参与白癜风发病机制进行了研究。然而，非节段性白癜风（NSV）患者血浆外泌体的miRNA表达谱尚未确定。
筛选NSV患者血浆外泌体中差异表达的微小RNA，并探讨其在NSV发病机制中的作用。
采用高通量测序确定NSV中外泌体miRNA的表达谱。使用各种分子生物学技术进一步研究NSV循环外泌体中上调的miR-1469对自然杀伤（NK）细胞的影响。
miR-1469被鉴定为一种候选生物标志物，其在NSV患者循环外泌体中的表达显著增加。循环外泌体被NK细胞内化，并通过传递miR-1469增加NK细胞增殖活力和IFN-γ分泌能力。进一步研究表明，miR-1469的预测靶标CD122的上调可部分逆转miR-1469对自然杀伤细胞的作用。
NSV患者血浆外泌体成分发生改变，似乎导致NK细胞功能障碍。外泌体miR-1469可能是疾病活动的生物标志物，可作为NSV患者先天免疫的治疗药物靶点。本研究为外泌体miRNA在NSV中的作用提供了新的见解，并提示了一种新的miR-1469-CD122-IFN-γ途径在NSV发病机制中的NK细胞作用。
