Abstract：
BACKGROUND: Elderly atopic dermatitis (AD) is a subtype of AD defined by age (≥ 60 years). The molecular characteristics of elderly AD remain to be clarified.
OBJECTIVE: We sought to characterize the molecular features of skin lesions and peripheral blood mononuclear cells (PBMCs) in patients with AD across different age, focusing on elderly AD.
METHODS: Skin and PBMCs samples were used for RNA sequencing. Analysis of differentially expressed genes and gene set variation analysis were performed. Immunofluorescence staining, quantitative real-time PCR (qRT-PCR), flow cytometry and transwell assay were used for validation.
RESULTS: Compared with healthy controls, the skin transcriptome of AD patients showed common signatures of AD, like barrier dysfunction and enhanced Th1/Th2/Th17 immune pathways. In PBMCs, the expression of Th1/Th2 response genes was more remarkable in adult AD, while expression of Th17-related genes was significantly higher in childhood AD. The gene modules associated with natural killer (NK) cells were downregulated in elderly AD. In skin lesions, elderly AD exhibited enrichment of macrophages, fibroblasts and senescence-associated secretory phenotype (SASP) related genes. The correlation among fibroblasts, SASP and innate immune cells were revealed by the co-localization of fibroblasts, macrophages and NK cells in the lesions across different age groups. Fibroblasts under inflammation or senescence could induce stronger chemotaxis of macrophages and NK cells.
CONCLUSIONS: We identified the molecular phenotypes of skin lesions and PBMCs in elderly AD individuals. Fibroblasts, innate immune cells, and SASP might play important roles in the pathogenesis of elderly AD.
OBJECTIVE: We sought to characterize the molecular features of skin lesions and peripheral blood mononuclear cells (PBMCs) in patients with AD across different age, focusing on elderly AD.
METHODS: Skin and PBMCs samples were used for RNA sequencing. Analysis of differentially expressed genes and gene set variation analysis were performed. Immunofluorescence staining, quantitative real-time PCR (qRT-PCR), flow cytometry and transwell assay were used for validation.
RESULTS: Compared with healthy controls, the skin transcriptome of AD patients showed common signatures of AD, like barrier dysfunction and enhanced Th1/Th2/Th17 immune pathways. In PBMCs, the expression of Th1/Th2 response genes was more remarkable in adult AD, while expression of Th17-related genes was significantly higher in childhood AD. The gene modules associated with natural killer (NK) cells were downregulated in elderly AD. In skin lesions, elderly AD exhibited enrichment of macrophages, fibroblasts and senescence-associated secretory phenotype (SASP) related genes. The correlation among fibroblasts, SASP and innate immune cells were revealed by the co-localization of fibroblasts, macrophages and NK cells in the lesions across different age groups. Fibroblasts under inflammation or senescence could induce stronger chemotaxis of macrophages and NK cells.
CONCLUSIONS: We identified the molecular phenotypes of skin lesions and PBMCs in elderly AD individuals. Fibroblasts, innate immune cells, and SASP might play important roles in the pathogenesis of elderly AD.
摘要：
背景：老年特应性皮炎（AD）是由年龄（≥60岁）定义的AD亚型。老年AD的分子特征仍有待阐明。
目的：我们试图表征不同年龄AD患者皮损和外周血单核细胞（PBMC）的分子特征，关注老年AD。
方法:皮肤和PBMC样品用于RNA测序。进行差异表达基因的分析和基因集变异分析。免疫荧光染色,实时定量PCR(qRT-PCR),流式细胞术和transwell分析用于验证。
结果：与健康对照组相比，AD患者的皮肤转录组显示出AD的共同特征，如屏障功能障碍和增强的Th1/Th2/Th17免疫途径。在PBMC中,Th1/Th2反应基因在成人AD中表达更为显著,而Th17相关基因的表达在儿童AD中显著增高。与自然杀伤（NK）细胞相关的基因模块在老年AD中下调。在皮肤损伤中，老年AD表现出巨噬细胞富集，成纤维细胞和衰老相关分泌表型（SASP）相关基因。成纤维细胞之间的相关性，SASP和先天性免疫细胞通过成纤维细胞的共定位来揭示，巨噬细胞和NK细胞在不同年龄组的病变。成纤维细胞在炎症或衰老状态下可以诱导巨噬细胞和NK细胞更强的趋化性。
结论：我们确定了老年AD患者皮损和PBMC的分子表型。成纤维细胞,先天免疫细胞，SASP可能在老年AD的发病机制中起重要作用。
目的：我们试图表征不同年龄AD患者皮损和外周血单核细胞（PBMC）的分子特征，关注老年AD。
方法:皮肤和PBMC样品用于RNA测序。进行差异表达基因的分析和基因集变异分析。免疫荧光染色,实时定量PCR(qRT-PCR),流式细胞术和transwell分析用于验证。
结果：与健康对照组相比，AD患者的皮肤转录组显示出AD的共同特征，如屏障功能障碍和增强的Th1/Th2/Th17免疫途径。在PBMC中,Th1/Th2反应基因在成人AD中表达更为显著,而Th17相关基因的表达在儿童AD中显著增高。与自然杀伤（NK）细胞相关的基因模块在老年AD中下调。在皮肤损伤中，老年AD表现出巨噬细胞富集，成纤维细胞和衰老相关分泌表型（SASP）相关基因。成纤维细胞之间的相关性，SASP和先天性免疫细胞通过成纤维细胞的共定位来揭示，巨噬细胞和NK细胞在不同年龄组的病变。成纤维细胞在炎症或衰老状态下可以诱导巨噬细胞和NK细胞更强的趋化性。
结论：我们确定了老年AD患者皮损和PBMC的分子表型。成纤维细胞,先天免疫细胞，SASP可能在老年AD的发病机制中起重要作用。
