Keratinocytes and neutrophils are important sources of proinflammatory molecules in hidradenitis suppurativa

Summary Background The pathogenesis of the chronic inflammatory skin disease hidradenitis suppurativa (HS, also known as acne inversa) involves epidermal alterations such as psoriasiform epidermal hyperplasia and keratin plugging. Keratinocytes are an important source of proinflammatory molecules in inflammatory skin diseases and can be stimulated by interleukin (IL)‐17+ cells. Objectives To explore the possible role of the epithelium in the pathogenesis of HS. Methods We performed immunohistochemical stainings and Western blot experiments to investigate the localization and expression of inflammation‐associated molecules, including the cytokine IL‐17, components of the inflammasome including caspase‐1, and the endogenous danger‐associated molecular pattern molecules S100A8 and S100A9 (calprotectin). To examine a possible effect of upregulated proinflammatory cytokines on the inflammatory infiltrate, differences in the cellular composition of perifollicular and deep dermal infiltrates were analysed. Results The number of IL‐17+ cells is increased in lesional and perilesional HS skin. The epidermis produces proinflammatory molecules and shows an upregulated expression of components of the NLRP3 inflammasome, activated caspase‐1 and expression of S100A8/S100A9. Additionally, the course of the inflammatory process in HS involves influx of innate immune cells, particularly IL‐17‐expressing neutrophils. Conclusions IL‐17‐producing cells are present in lesional and perilesional HS skin and may contribute to the initiation of inflammatory processes. Furthermore, the epidermis is a source of proinflammatory cytokines, shows inflammasome activation and expresses S100A8/S100A9, thereby possibly contributing to the propagation of inflammation. A massive influx of IL‐17‐expressing neutrophils is observed in the deep infiltrate. What's already known about this topic? The proinflammatory cytokines interleukin (IL)‐17 and IL‐1β are upregulated in lesional skin of patients with hidradenitis suppurativa (HS). The endogenous danger‐associated molecular pattern molecules S100A8 and S100A9 are elevated in the serum of patients with HS. What does this study add? IL‐17+ cells are present in perilesional skin of patients with HS. NLRP3 expression is enhanced and the inflammasome is activated in lesional epidermis of HS. S100A8 and S100A9 are upregulated in lesional HS epidermis. Infiltrating neutrophils are a source of IL‐17, thereby sustaining the inflammatory process. Linked C