What is it about?
Hidradenitis suppurativa (HS) is a chronic, severe and recurrent inflammatory skin disease with poorly described underlying molecular mechanism. HS is characterized by a complex heterogenous histologic phenotype, that includes epidermal psoriasiform hyperplasia, follicular occlusion and hyperkeratosis, immune cell infiltration, dermal fibrosis, and the development of epithelialized sinus tract. HS also leads to pain, malodorous discharge, and impression during the disease progression and affects both physical and mental health on patients. Adalimumab (ADA), a monoclonal antibody targeting TNF-α, is currently the US Food and Drug Administration (FDA) approved biologic drug for the treatment of moderate-to-severe HS. However, surgical resection of affected tissue remains the ultimate option for patients who do not respond to available treatments. Here, we delineated the reprogrammed transcriptional profiles in HS basal stem/progenitor cells and discovered two keratinocyte populations that trigger IL1, IL10, and complement inflammatory cascades in HS. We further revealed novel genome-wide chromatin altered regions alongside the switch of transcription factors, which highly mediated HS transcriptional profiles. The disruption of the certain inflammation-related chromatin regions using CRISPR/Cas9-mediated approach or the pharmacological inhibition of the interferon regulatory transcription factor 3 (IRF3) efficiently reduced the production of HS-associated inflammatory regulators.
Featured Image
Photo by Romina Farías on Unsplash
Why is it important?
In this study, we elucidated the epigenetic mechanisms underlying the pathogenic plasticity of basal progenitors in HS skin, which adds another layer of understanding of epithelial cell reprogramming in the context of chronic inflammatory skin diseases. Translationally, targeting inflammatory enhancers and key TFs could complement current biological drug-based therapies and pave the way for precision medicine in HS.
Perspectives
Hidradenitis suppurativa was first reported by Alfred-Armand-Louis-Marie Velpeau in 1839. To date, little is known about its original pathogenesis. It was a great pleasure that our team contributed to reveal the truth of this complicated disease. I hope that our contemporary biologists and dermatologists together will unveil its mystery using the state-of-the -art technology and innovated models in the future.
Lin Jin
University of Alabama at Birmingham
Read the Original
This page is a summary of: Epigenetic switch reshapes epithelial progenitor cell signatures and drives inflammatory pathogenesis in hidradenitis suppurativa, Proceedings of the National Academy of Sciences, November 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2315096120.
You can read the full text:
Contributors
The following have contributed to this page
