Aberrant expression of interleukin-17A in mast cells contributes to the pathogenesis of hidradenitis suppurativa

Background Hidradenitis suppurativa (HS) significantly diminishes the quality of life for patients. Delayed diagnosis represents a significant challenge in effectively managing HS. Objectives To identify and characterize the key mediator in HS. Methods Bioinformatic transcriptomic analysis was applied to identify potential candidates contributing to the disease process of HS. Skin samples from 40 patients with HS, four with psoriasis and 29 with normal skin were included. The expression of interleukin (IL)-17A was evaluated and compared among samples of normal skin, psoriatic skin and skin from different stages of HS by immunohistochemistry or dualcolour immunofluorescence. In vitro experiments and RNA sequencing analysis were also conducted to validate the expression of IL-17A and its pathogenic effect in HS. Results Transcriptomic database analyses identified IL-17 signalling as a potential contributor to HS. In HS, the predominant IL-17A⁺ cell population was identified as mast cells. IL-17A⁺ mast-cell density was significantly elevated in HS, especially in samples with advanced Hurley stages, compared with normal skin and psoriasis samples. The close contact between IL-17A⁺ mast cells and IL-17 receptor A (IL-17RA)- expressing keratinocytes was demonstrated, along with the significant effects of IL-17A on keratinocyte cell proliferation and HS pathogenic gene expression. Treatment with biologics (brodalumab or adalimumab) reduced the severity of the disease and the number of IL-17A⁺ mast cells in affected tissues. Conclusions The presence of high-density IL-17A⁺ mast cells may serve as a valuable pathological marker for diagnosing HS. Moreover, developing therapeutic drugs targeting IL-17A⁺ mast cells may provide a new approach to treating HS.