The polygenic architecture of hidradenitis suppurativa reveals signaling mechanisms that implicate epithelial remodeling.

ABSTRACT: We sought to identify clinically relevant regulators of hair follicle inflammation by conducting a human genetic study of hidradenitis suppurativa (HS), a prevalent, understudied, inflammatory disease with limited effective treatments. We performed a GWAS with 6,300 cases and identified 12 independent risk loci. Epigenetic and transcriptomic analyses of HS risk variants defined cell-specific gene regulatory programs. We experimentally validated a coherent gene module defined by upregulated SOX9 , CXCR4 , and CD74 co-expression that maps to aberrant epithelial structures in the skin. Pharmacological inhibition of CXCR4 implicates CD74 mediated regulation of PI3K/AKT and NF-κB signaling to calibrate inflammation, proliferation and apoptosis in keratinocytes. We next used

SUBMITTER: Khan A 

PROVIDER: S-EPMC12324615 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature