Single-cell transcriptomics reveals key cell types, pathways and targets in skin tissue associated with HS and PPP

Abstract

Abstract Motivation: The skin is of paramount importance to human health and well-being due to its multifaceted roles such as biophysical and immunological protection through a complex cellular network established early in embryonic development. Inflammatory skin diseases encompass a diverse group of conditions characterized by dysregulated immune responses and inflammation within the skin. In this study, we used single-cell RNA sequencing to profile the transcriptomes of in total 23 skin biopsies from patients with pustular psoriasis (PSO), hidradenitis suppurativa (HS), and palmoplantar pustulosis (PPP). Analyzing skin inflammation at the single-cell transcriptomic level is essential for uncovering the molecular mechanisms and cellular crosstalk that drive the inflammatory response in the skin. This knowledge is crucial for designing targeted therapies that can improve patient outcomes, while also providing insights into the common and distinct patterns among these diseases, which can aid in the development of more specialized treatments. By profiling individual cells from skin biopsies, the study identified distinct cellular populations, signaling pathways and cellular crosstalk that may contribute to the pathogenesis of these conditions. The analysis highlights the heterogeneity within and between disease states, with a particular focus on immune cell dynamics and interactions within the skin's microenvironment. Results: These datasets were leveraged to compare cell states across the three mentioned diseases. Key findings include the identification of significant differences in cell type composition across the diseases, with B cells and neutrophils showing distinct patterns of abundance. Additionally, ligand-receptor interaction analysis revealed potential signaling pathways, such as those involving TGFβ1, that could play crucial roles in disease progression. The IL-36 cytokine family exhibited diseasespecific expression, with PSO showing a pronounced inflammatory profile. Additionally, differential expression of key cytokines and chemokines highlighted potential molecular drivers of inflammation in these conditions. The study emphasizes the utility of scRNA-seq in uncovering disease-specific cellular behaviors and molecular targets, providing insights that could inform future therapeutic strategies.