The Multifaceted Role of Keratinocytes in Hidradenitis Suppurativa Pathogenesis

Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin disorder of the pilosebaceous unit, with multiple factors contributing to its onset, activity and progression. Alongside a predisposing genetic background, hormonal and microbiome alterations, dysregulation of innate and adaptive immune response, as well as environmental/epigenetic factors contribute to its immunopathogenic landscape. In the past years, translational investigations identified several distinct inflammatory networks, not only in the chronic but also in the early stages of disease, making them potential therapeutic targets. Emerging evidence underlies the important role of keratinocytes in the pathogenesis and progression of HS, acting not only as targets of inflammatory signaling pathways but also as active producers of pro-inflammatory cytokines, chemokines and effector molecules that may influence disease onset and activity. Despite these insights, different aspects of their involvement remain underexplored, necessitating further targeted research. This review aims to highlight the experimental evidence supporting the crucial role of keratinocytes in the inflammatory response and overall pathophysiology of HS.