Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa

How transcription factors (TFs) regulate stem cells to maintain homeostasis, how noncoding single nucleotide variants (SNVs) linked to polygenic disease risk relate to such TFs, and the target genes SNVs dysregulate are central questions in stem cell and polygenic disease research. Massively parallel reporter gene analysis (MPRA) of 3,451 SNVs linked to risk for prevalent human skin diseases identified 355 differentially active SNVs (daSNVs). daSNV target gene analysis, including daSNV gene editing, highlighted dysregulated epidermal differentiation as a common pathomechanism. CRISPR knockout screens of 1772 human TFs identified 108 TFs essential for the control of epidermal differentiation, validating new roles for ZNF217, CXXC1, FOXJ2, IRX2 and NRF1. Population sampling CUT&RUN of 27 homeostatic TFs identified allele-specific binding (ASB) differences enriched near epidermal homeostasis and monogenic skin disease genes, with prominent representation of SP/KLF and AP-1/2 TFs. This resource implicates dysregulated differentiation in pathogenic risk for diverse polygenic skin diseases.

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Unlocking the Mechanisms of Hidradenitis Suppurativa: Inflammation and miRNA Insights

Ames,

Sanders,

Jacobs

et al. 2024

CCID

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Inflammatory skin diseases impose a significant burden on patients and healthcare systems worldwide. Among these, hidradenitis suppurativa (HS) is particularly notable for its chronic and recurrent nature. Recurrent nodules, abscesses, and scarring in apocrine gland-rich areas characterize the disease, including the groin, axillae, and perianal regions. Despite its considerable physical and psychological impact, the precise mechanisms driving HS remain elusive. Recent advancements in understanding the inflammatory processes involved in HS have highlighted the TNF-alpha, IL-1β, and IL-17/IL-23 pathways, which play crucial roles in initiating and perpetuating the disease. Moreover, specific microRNAs (miRNAs), such as miR-24-1-5p, miR146a-5p, mirR-26a-5p, miR-206, miR-338-3p, and miR-338-5p, are involved in these inflammatory processes. Dysregulation of these miRNAs contributes to aberrant cytokine expression and persistent inflammation, foreseeably exacerbating HS disease progression. This narrative review hypothesizes that miRNA dysregulation triggers aberrant expression in specific inflammatory pathways, contributing to HS’s clinical manifestations and progression. We explore the implicated miRNAs’ potential as biomarkers for earlier disease detection and as novel therapeutic targets. Identifying miRNA dysregulation offers new opportunities for earlier and more accurate diagnosis, potentially allowing clinicians to intervene before severe disease manifestations occur. Furthermore, therapeutic strategies to modulate miRNA expression could target the inflammatory pathways driving HS, leading to more personalized and effective treatments. This review also discusses future research directions to enhance the clinical management of HS. A better understanding of miRNA involvement in HS offers new avenues for research and management, ultimately improving patient outcomes and quality of life.

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Therapeutic Potential of IL-1 Antagonism in Hidradenitis Suppurativa

Cited by 4 publications

References 63 publications

Publication trends and research hotspots of IL-1: A bibliometric analysis of IL-1 with relevance to anesthesia in highly cited papers from WoSCC

Publication trends and research hotspots of IL-1: A bibliometric analysis of IL-1 with relevance to anesthesia in highly cited papers from WoSCC

Disease-Linked Regulatory DNA Variants and Homeostatic Transcription Factors in Epidermis

Unlocking the Mechanisms of Hidradenitis Suppurativa: Inflammation and miRNA Insights

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