Transcriptomic Study Identifies IL-1β Axis in Hidradenitis Suppurativa

Comprehensive transcriptomic profiling of hidradenitis suppurativa (HS) highlights a dominant macrophage-derived IL-1β/NLRP3 inflammasome axis, providing new insight into disease pathogenesis and potential therapeutic targets, according to research presented by Andrea Daamen, PhD, at the American Academy of Dermatology (AAD) 2026 Annual Meeting.

HS is a chronic inflammatory disease characterized by painful nodules and abscesses, with complex and heterogeneous underlying biology.

“HS pathology has frequently been associated with dysfunctional hair follicles,” Dr. Daamen said. “One of the molecular abnormalities that has been proposed as a potential driver of HS immune pathology and inflammation is increased production ofIL-1 beta.”

Using bulk RNA sequencing from paired lesional and non-lesional skin across multiple cohorts, investigators identified consistent enrichment of IL-1β, IL-18, and NLRP3 inflammasome–related gene sets in HS lesions, alongside reductions in barrier and adhesion pathways. Comparative analyses showed that psoriasis and related dermatoses demonstrated more prominent IL-23/IL-36–driven T helper 17 activity, while atopic dermatitis exhibited type 2–dominant signatures with relatively low IL-1 activity.

To further localize inflammatory drivers, single-cell RNA sequencing revealed that IL-1β expression was concentrated primarily in macrophages, with additional expression in tissue stem cells.

“Expression of IL-1 beta was almost solely concentrated to macrophages,” Daamen noted, while its receptor, IL-1R1, was broadly expressed across myeloid and stromal compartments. 

The study also demonstrated upregulation of the NLRP3 inflammasome complex, which is required for activation of IL-1β, suggesting coordinated pathway activation at both transcriptional and functional levels.

These findings position HS as a distinct inflammatory dermatosis characterized by a macrophage-centered IL-1 axis, differentiating it from other conditions with overlapping clinical features.

“This macrophage-derived IL-1β/NLRP3 inflammasome axis is a promising therapeutic target for HS,” Daamen said. 

The poster concluded that these data support the development of IL-1–based biomarkers and biomarker-guided therapeutic strategies, with potential implications for patient stratification in future clinical trials.