Hair follicle stem cell fate supports distinct clinical endotypes in hidradenitis suppurativa.

ABSTRACT:

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting approximately 1% of the global population. Its pathogenesis involves both aberrant keratinization and autoinflammation, but the temporal relationship between these processes remains unclear.

Objectives

To investigate the role of HF stem cell (HF-SC) fate in the early pathogenesis of HS.

Methods

We performed single-cell RNA sequencing of HF cell populations from HS patients and healthy donors. We then analysed HF cell composition isolated from perilesional skin of 49 HS patients and integrated these data with clinical phenotypes to define disease endotypes.

Results

Our data revealed two distinct differentiation trajectories of HF stem cells (HF-SCs): one leading to interfollicular epidermis (IFE) basal cells enriched in inflammatory pathways, and another giving rise to outer root sheath (ORS) cells associated with keratinization. In HS lesions, both populations displayed altered inflammatory phenotypes and were closely linked to immune cell infiltration, pointing to a role in disease heterogeneity. By integrating clinical features with HF cell composition from 49 HS patients, we identified three major endotypes: (i) an inflammatory subtype, marked by T cell infiltration and an expansion of IFE basal cells; (ii) a keratinizing subtype, characterized by ORS enrichment and minimal inflammation; and (iii) a mixed subtype, exhibiting features of follicular remodelling, fistula formation and variable immune involvement.

Conclusions

These findings provide novel insights into the epithelial-immune interactions that drive HS and support a stratified therapeutic approach tailored to distinct epithelial dysfunctions.

SUBMITTER: Onfroy A 

PROVIDER: S-EPMC12933698 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature