Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Int Immunopharmacol. 2020 Jul;84:106544. doi: 10.1016/j.intimp.2020.106544. Epub 2020 Apr 27.
Alopecia areata (AA) is a common alopecia characterized by non-scarring hair loss with the dysregulated immunity. However, the pathogenesis of AA remains to be elucidated. In this study, we identified gene signatures and then analyzed transcription factor-immune regulatory network in AA using integrated bioinformatics methods. Finally, we verified potential target genes in lesions of AA patients using qPCR and immunohistochemistry. Here, 74 differentially expressed genes (DEGs) were identified in AA, which were enriched in immune-related signaling pathway. The immune analysis revealed the infiltration of γδT cells and Macrophages M1 in AA lesion. Next, the expression correlation analysis and ChIP-seq results revealed a transcription factor (EOMEs) regulated network. We found that EOMEs, a T-box transcription factor, may be involved in the immunoregulation in AA via targeting CD8A and BMP2, and it may affect keratinocytes function via regulating GZMK, LYPD6, RNF182, KRTAP5-9 and KRT73 expression. Finally, the mRNA expression of these network genes in AA lesions was confirmed using qPCR. And the increase expression of EOMEs was identified at inflammatory cells at the periphery of hair follicles and partial keratinocytes in AA tissue using immunohistochemistry. In conclusions, our research demonstrated that EOMEs may play a key role in the progression of AA via regulating immune cell infiltration and keratinocytes function, indicating EOMEs as a promising therapeutic target of AA.
斑秃(AA)是一种常见的脱发疾病,其特征为非瘢痕性脱发和免疫失调。然而,AA 的发病机制仍有待阐明。在本研究中,我们通过整合生物信息学方法,鉴定了 AA 中的基因特征,并分析了转录因子-免疫调节网络。最后,我们通过 qPCR 和免疫组织化学验证了 AA 患者病变中的潜在靶基因。本研究中,我们共鉴定了 74 个差异表达基因(DEGs),这些基因富集于免疫相关信号通路。免疫分析显示,γδT 细胞和 M1 巨噬细胞浸润在 AA 病变中。接下来,通过表达相关性分析和 ChIP-seq 结果,揭示了一个转录因子(EOMEs)调控网络。我们发现,T 盒转录因子 EOMEs 可能通过靶向 CD8A 和 BMP2 参与 AA 的免疫调节,通过调节 GZMK、LYPD6、RNF182、KRTAP5-9 和 KRT73 的表达影响角质形成细胞的功能。最后,我们通过 qPCR 验证了这些网络基因在 AA 病变中的表达。免疫组织化学结果显示,EOMEs 在毛囊周围炎症细胞和 AA 组织中的部分角质形成细胞中呈高表达。综上所述,我们的研究表明,EOMEs 可能通过调节免疫细胞浸润和角质形成细胞功能在 AA 的进展中发挥关键作用,提示 EOMEs 是治疗 AA 的一个有前途的靶点。