Identification and verification of EOMEs regulated network in Alopecia areata

• Published in: International immunopharmacology Vol. 84; p. 106544
• Main Authors: Yuan, Xin, Tang, Yan, Zhao, Zhixiang, Liu, Fangfen, Shi, Wei, Zhang, Yiya, Li, Ji
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2020; Elsevier BV
• Subjects: Adolescent; Adult; Alopecia; Alopecia areata; Alopecia Areata - genetics; Baldness; Bioinformatics; Bioinformatics analysis; Computer programs; Correlation analysis; Disease Progression; EOMEs; Female; Follicles; Gene expression; Genes; Hair; Hair Follicle - immunology; Humans; Immune system; Immunohistochemistry; Immunoregulation; Infiltration; Inflammation; Intraepithelial Lymphocytes - immunology; Keratinocytes; Keratinocytes - immunology; Keratinocytes function; Lesions; Macrophages; Macrophages - immunology; Male; Middle Aged; Pathogenesis; Protein Interaction Maps; Scars; Signal transduction; T-Box Domain Proteins - genetics; T-Box Domain Proteins - immunology; Transcription factor; Transcription factors; Transcriptome; Young Adult; Bioinformatics analysis; EOMEs; Transcription factor; Immunoregulation; Keratinocytes function; Alopecia areata
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106544

•74 differentially expressed genes (DEGs) were identified in AA, which were enriched in immune-related signaling pathway.•The infiltration of γδT cells and Macrophages M1 increased in AA lesion.•EOMEs may play a key role in the progression of AA via regulating immune cell infiltration and keratinocytes function. 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.