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

Authors: Peter Seiringer*, Christina Hillig*, Alexander Schäbitz, Manja Jargosch, Anna Caroline Pilz, Stefanie Eyerich, Andrea Szegedi, Michaela Sochorová, Florian Gruber, Christos C Zouboulis, Tilo Biedermann, Michael Menden†, Kilian Eyerich†, Daniel Törőcsik†

*contributed equally as first authors
†contributed equally as last authors

Summary

Spatial transcriptomics of psoriasis and atopic dermatitis revealed that sebaceous glands consistently express lipid metabolism genes and the inflammation marker SAA1. Atopic dermatitis showed lipid-focused changes, while psoriasis displayed stronger inflammatory signatures including keratinization, neutrophil degranulation, and antimicrobial pathways. These results indicate sebaceous glands actively modulate inflammation in a disease-specific manner.

Spatial Transcriptomics Analysis of Sebaceous Glands

• Data

  • 6 lesional vs. non-lesional skin samples from psoriasis and atopic dermatitis patients (~26k transcriptomes; 212 spots annotated as sebaceous glands).

• Pipeline

  • Manual annotation → SpatialDE (SVG detection) → DEG analysis → Pathway enrichment.

• Non-Lesional Skin

  • SGs identified by 5,449 DEGs.
  • Four spatial patterns significantly enriched (patterns 1, 7, 8, 9).
  • Key pathways: lipid/fatty acid/steroid/cholesterol metabolism and energy (pattern 9); mitochondrial/citric acid cycle, transport, cell cycle (patterns 1 & 7).

• Lesional Skin Insights

  • Both AD and PSO: High expression of lipid metabolism/transport genes (ALOX15B, APOC1, FABP7, FADS1/2, FASN, PPARG, RARRES1) + inflammation-related SAA1.
  • AD-specific: ACAD8, FADS6, EBP, HSD3B1, CCL17 (lipid/Th2-inflammation related).
  • PSO-specific: SERPINF1, FKBP5, IFIT1/3, DDX58, ACOT4, S1PR3 (inflammatory/lipid) + keratinization and antimicrobial gene programs.

• Pathway Enrichment Highlights

  • AD SGs: Cholesterol, fatty acid, steroid metabolism.
  • PSO SGs: Keratinization, antimicrobial peptides, neutrophil degranulation.
  • PSO vs. AD: Increased interferon signaling, keratinization, antimicrobial responses.