Wenxuan Bai , Le Yang , Jing Qiu , Zihan Zhu , Shuxing Wang , Peidi Li , Dawei Zhou , Hongyi Wang , Yuxuan Liao , Yao Yu , Zijiang Yang , Puqiao Wen , Di Zhang
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We then identified 13 hub genes with a strong association with CD4<sup>+</sup> T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4<sup>+</sup> T subcluster, CD4<sup>+</sup> tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4<sup>+</sup> TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4<sup>+</sup> TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (<em>p</em> < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4<sup>+</sup> TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4<sup>+</sup> TRM may be involved in the pathogenesis of adult AD.</p></div>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000910/pdfft?md5=8c01709a6dbe732533a5bd68d7a74b2c&pid=1-s2.0-S0888754324000910-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: A new potential mechanism\",\"authors\":\"Wenxuan Bai , Le Yang , Jing Qiu , Zihan Zhu , Shuxing Wang , Peidi Li , Dawei Zhou , Hongyi Wang , Yuxuan Liao , Yao Yu , Zijiang Yang , Puqiao Wen , Di Zhang\",\"doi\":\"10.1016/j.ygeno.2024.110870\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The pathophysiology of atopic dermatitis (AD) is complex. CD4<sup>+</sup> T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4<sup>+</sup> T memory cells (<em>p</em> < 0.01). We then identified 13 hub genes with a strong association with CD4<sup>+</sup> T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4<sup>+</sup> T subcluster, CD4<sup>+</sup> tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4<sup>+</sup> TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4<sup>+</sup> TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (<em>p</em> < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4<sup>+</sup> TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. 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引用次数: 0
摘要
特应性皮炎(AD)的病理生理学非常复杂。CD4+ T 细胞在特应性皮炎的病变发展过程中起着至关重要的作用。然而,其潜在机制仍不清楚。在本研究中,我们利用基因表达总库(GEO)数据库中的两个数据集研究了成人特应性皮炎病变皮肤和非病变皮肤之间的差异表达基因(DEGs)。结果显示,62个DEG与细胞因子反应有关。与无病变皮肤相比,病变皮肤显示出免疫浸润,活化的自然杀伤(NK)细胞和 CD4+ T 记忆细胞(使用加权相关网络分析的 p + T 细胞)数量增加。AD 的单细胞分析检测到了一种新型的 CD4+ T 亚群,即 CD4+ 组织驻留记忆细胞(TRMs),并通过免疫组化(IHC)验证了这种细胞在 AD 的真皮区域有所增加。进一步的分析评估了 CD4+ TRM 与 AD 之间的重要关系。定量聚合酶链反应(qPCR)显示,13 个枢纽基因中的两个基因 FOXO1 和 SBNO2 在 CD4+ TRM 中表达,但在 IFN-γ/TNF-α 诱导的 HaCaT 细胞中却下调。此外,SBNO2 的表达与 AD(p + TRM)中 Th1 细胞浸润的增加有关,并且在 IFN-γ/TNF-α 诱导的 HaCaT 细胞中高表达(使用 qPCR 和 Western 印迹法测定)。总之,我们的研究结果表明,新发现的CD4+ TRM可能参与了成人AD的发病机制。
Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: A new potential mechanism
The pathophysiology of atopic dermatitis (AD) is complex. CD4+ T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4+ T memory cells (p < 0.01). We then identified 13 hub genes with a strong association with CD4+ T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4+ T subcluster, CD4+ tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4+ TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4+ TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (p < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4+ TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4+ TRM may be involved in the pathogenesis of adult AD.