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

Front Immunol. 2024 Feb 16:15:1334844. doi: 10.3389/fimmu.2024.1334844. eCollection 2024.

Abstract

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.

Keywords: atopic dermatitis (AD); inflammatory skin diseases; lipid metabolism; psoriasis; sebaceous glands; spatial transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dermatitis, Atopic* / genetics
  • Gene Expression Profiling
  • Humans
  • Inflammation / genetics
  • Lipid Metabolism / genetics
  • Membrane Proteins
  • Psoriasis* / genetics
  • Sebaceous Glands
  • Transcriptome

Substances

  • RARRES1 protein, human
  • Membrane Proteins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Hungarian National Research, Development and Innovation Office FK-132296 and ANN 139589 (DT), by Hans und Klementia Langmatz Stiftung, Garmisch-Partenkirchen, Germany (PS), the Federal Ministry for Digital and Economic Affairs of Austria and the National Foundation for Research, Technology, and Development of Austria to the Christian Doppler Laboratory for Skin Multimodal Imaging of Aging and Senescence (MS, FG), and by Deutsche Forschungsgemeinschaft (DFG) through TUM International Graduate School of Science and Engineering (IGSSE), GSC 81 (CH, MPM, SE) and RTG2668 Project A1 & A2, Project-ID: 435874434 (SE, TB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.