What is it about?

Hidradenitis suppurativa (HS) is a chronic debilitating skin disease with high levels of suffering for the affected patients, but limited treatment options. Keratinocyte dysfunction has previously been suggested as a key factor in the development and chronification of the disease, but the precise contribution of keratinocytes to the generation of the necessary innate and adaptive immune signals is unclear. Through RNA sequencing of matching perilesional and lesional epidermis of patients, we show that the lesional epidermis is characterized by a strong keratinocytic stress signature dominated by AP1-driven gene expression and pronounced JAK/STAT1 activation.

Featured Image

Why is it important?

What's new: • Lesional epidermis of HS patients is characterized by a strong keratinocytic stress signature dominated by an AP1-driven gene expression pattern and marked JAK/STAT1 activation in active lesions, which promotes expression of key inflammatory genes of the innate immune response and T cell activation • Treatment of patient-derived keratinocytes with IFN gamma leads to persistent STAT1 phosphorylation and can recapitulate the expression of important immunomodulatory genes that are upregulated in HS lesions. • Induction of several of these epidermal immune-regulatory genes is further enhanced by IFN-gamma/TNF co-stimulation but can be completely abrogated by pharmacological JAK1 inhibition, suggesting that JAK/STAT1 inhibitors, alone or in combination with clinically used TNF-antagonists could be a potentially promising treatment option for HS patients

Perspectives

Given the often unsatisfactory response of HS patients to the currently only approved targeted therapy with an anti-TNFα antagonist, manipulation of the JAK/STAT1 signaling pathway could be a potentially promising new approach for the treatment of HS patients.

Professor Marc Schmidt
University of Würzburg

Read the Original

This page is a summary of: Stress signaling and STAT1 activation characterize the keratinocytic gene expression pattern in Hidradenitis suppurativa, Journal of the European Academy of Dermatology and Venereology, July 2022, Wiley,
DOI: 10.1111/jdv.18465.
You can read the full text:

Read

Resources

Contributors

The following have contributed to this page