Stress Signaling and STAT1 Activation Play Key Role in Disease Progression of Hidradenitis Suppurativa

According to a study published in The Journal of the European Academy of Dermatology and Venereology, stress signaling and JAK/STAT1 activation play a key role in disease progression of hidradenitis suppurativa (HS). Possible interference with JAK/STAT1 signals could potentially serve as a therapeutic approach for HS.

Researchers aimed to analyze the role of keratinocytes in HS lesion formation by comparing the transcriptomes of lesional and perilesional epidermis isolated from patients with HS by RNA sequencing (RNA-Seq). They obtained samples from 5 different donors with HS who were pairwise matched lesional and perilesional. Epidermal keratinocytes were also isolated and processed for RNA extraction and RNA-Seq. Utilizing the large-scale promoter analysis and functional annotation clustering, researchers analyzed lesionally regulated genes to identify epidermally overrepresented transcription factor binding sites and functionally related gene groups.

The results showed that HS is characterized by a strong epidermal stress state due to significant overrepresentation of an AP-1-driven gene signature and with an immense activation of the stress-activated c-Jun N-terminal kinase (JNK) pathway in lesional epidermis.

“Additionally, our data reveal a strong induction of STAT1 activation in lesional HS epidermis that likely results from IFNγ production and triggered expression of key inflammatory genes coordinating innate immune activation and the adaptive T cell response in HS,” the authors concluded.

Reference
Frings VG, Jopp L, Srivastava M, et al. Stress signaling and STAT1 activation characterize the keratinocytic gene expression pattern in hidradenitis suppurativa. J Eur Acad Dermatol Venereol. Published online July 26, 2022. doi:10.1111/jdv.18465