Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With M1 Macrophage Polarization in Hidradenitis Suppurativa

Paula Mariottoni, Simon W. Jiang, Courtney A. Prestwood, Vaibhav Jain, Jutamas Suwanpradid, Melodi Javid Whitley, Margaret Coates, David A. Brown, Detlev Erdmann, David L. Corcoran, Simon G. Gregory, Tarannum Jaleel, Jennifer Y. Zhang, Tamia A. Harris-Tryon, Amanda S. MacLeod

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment.

Original languageEnglish (US)
Article number665873
JournalFrontiers in Medicine
Volume8
DOIs
StatePublished - Aug 24 2021

Keywords

  • antiviral immune pathways
  • hidradenitis suppurativa
  • interferon
  • macrophage-cell
  • non-healing wounds
  • single cell sequencing

ASJC Scopus subject areas

  • Medicine(all)

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