Table_4_Spatial transcriptomics reveals altered lipid metabolism and inflammation-related gene expression of sebaceous glands in psoriasis and atopic dermatitis.xlsx

Sebaceous glands drive acne, however, their role in other inflammatory skin diseases remains unclear. To shed light on their potential contribution to disease development, we investigated the spatial transcriptome of sebaceous glands in psoriasis and atopic dermatitis patients across lesional and non-lesional human skin samples. Both atopic dermatitis and psoriasis sebaceous glands expressed genes encoding key proteins for lipid metabolism and transport such as ALOX15B, APOC1, FABP7, FADS1/2, FASN, PPARG, and RARRES1. Also, inflammation-related SAA1 was identified as a common spatially variable gene. In atopic dermatitis, genes mainly related to lipid metabolism (e.g. ACAD8, FADS6, or EBP) as well as disease-specific genes, i.e., Th2 inflammation-related lipid-regulating HSD3B1 were differentially expressed. On the contrary, in psoriasis, more inflammation-related spatially variable genes (e.g. SERPINF1, FKBP5, IFIT1/3, DDX58) were identified. Other psoriasis-specific enriched pathways included lipid metabolism (e.g. ACOT4, S1PR3), keratinization (e.g. LCE5A, KRT5/7/16), neutrophil degranulation, and antimicrobial peptides (e.g. LTF, DEFB4A, S100A7-9). In conclusion, our results show that sebaceous glands contribute to skin homeostasis with a cell type-specific lipid metabolism, which is influenced by the inflammatory microenvironment. These findings further support that sebaceous glands are not bystanders in inflammatory skin diseases, but can actively and differentially modulate inflammation in a disease-specific manner.

皮脂腺是痤疮的致病驱动因素，但其在其他炎症性皮肤病中的作用仍未明确。为阐明皮脂腺在疾病发生发展中的潜在贡献，我们对银屑病（psoriasis）与特应性皮炎（atopic dermatitis）患者的皮损及非皮损皮肤样本中的皮脂腺空间转录组（spatial transcriptome）开展了分析。研究发现，特应性皮炎与银屑病患者的皮脂腺均表达编码脂质代谢与转运关键蛋白的基因，涵盖ALOX15B、APOC1、FABP7、FADS1/2、FASN、PPARG及RARRES1。此外，炎症相关基因SAA1被鉴定为两类疾病中共有的空间可变基因。在特应性皮炎患者中，主要与脂质代谢相关的基因（如ACAD8、FADS6或EBP）以及疾病特异性基因——即与Th2炎症相关的脂质调控基因HSD3B1——均呈现差异表达。与之相对，在银屑病患者中则鉴定出更多炎症相关的空间可变基因，例如SERPINF1、FKBP5、IFIT1/3及DDX58。银屑病特异性富集的其他通路还包括脂质代谢（如ACOT4、S1PR3）、角质形成（如LCE5A、KRT5/7/16）、中性粒细胞脱颗粒以及抗菌肽相关通路（如LTF、DEFB4A、S100A7-9）。综上，本研究结果表明，皮脂腺通过细胞类型特异性的脂质代谢参与维持皮肤稳态，且该过程受炎症微环境调控。上述研究结果进一步证实，皮脂腺并非炎症性皮肤病中的旁观者，而是能够以疾病特异性方式主动、差异化地调控炎症进程。