Cigarette smoke underlies the pathogenesis of palmoplantar pustulosis via an IL-17A-induced production of IL-36γ in tonsillar epithelial cells.

Abstract Palmoplantar pustulosis (PPP) is characterized by sterile pustules on the palms and/or soles. A strong association between PPP and tobacco smoking has been reported, and it has been speculated that the interleukin (IL)-17A pathway may play an important role in PPP. Recent studies have suggested that IL-36 plays a pivotal role in the pathogenesis of psoriasis and its subtypes. The relationships among IL-36, smoking, and PPP have not been examined. Here, we investigated the relationships among the smoking index, severity of the clinical condition of PPP, and in vitro dynamics of IL-36 in human tonsillar epithelial cells under the condition of exposure to a cigarette smoke extract (CSE). The results demonstrated that the Palmoplantar Pustulosis Area and Severity Index (PPPASI) was strongly and positively correlated with the smoking index in female patients. Immunohistochemical examinations showed that IL-36γ was highly expressed in tonsillar epithelial cells from PPP patients but not in those from recurrent tonsillitis patients without PPP. The in vitro study revealed that IL-17A synergistically induced a release of IL-36γ under CSE exposure. These results suggest that local production of IL-36γ by epithelial cells induced by cigarette smoke exposure plays an important role in the pathogenesis of PPP.