Characterisation of IL‐1 family members in Sweet syndrome highlights the overexpression of IL‐1β and IL‐1R3 as possible therapeutic targets

Calabrese, Laura ; Ney, Francesca; Aoki, Rui ; Moltrasio, Chiara; Marzano, Angelo V.; Kerl, Katrin; Stadler, Pia‐Charlotte; Satoh, Takashi K. und French, Lars E. (2023): Characterisation of IL‐1 family members in Sweet syndrome highlights the overexpression of IL‐1β and IL‐1R3 as possible therapeutic targets. In: Experimental Dermatology, Bd. 32, Nr. 11: S. 1915-1923

Abstract

Sweet syndrome (SS) as a prototypic neutrophilic dermatosis (NDs) shares certain clinical and histologic features with monogenic auto-inflammatory disorders in which interleukin (IL)-1 cytokine family members play an important role. This has led to the proposal that NDs are polygenic auto-inflammatory diseases and has fuelled research to further understand the role of IL-1 family members in the pathogenesis of NDs. The aim of this study was to characterise the expression of the IL-1 family members IL-1β, IL-36γ, IL-33 and IL-1R3 (IL-1RaP) in SS. The expression profile of IL-1β, IL-33, IL-36γ and their common co-receptor IL-1R3 was analysed by immunohistochemistry, in situ hybridisation and double immunofluorescence (IF) in healthy control skin (HC) and lesional skin samples of SS. Marked overexpression of IL-1β in the dermis of SS (p < 0.001), and a non-significant increase in dermal (p = 0.087) and epidermal (p = 0.345) IL-36γ expression compared to HC was observed. Significantly increased IL-1R3 expression within the dermal infiltrate of SS skin samples (p = 0.02) was also observed, whereas no difference in IL-33 expression was found between SS and HC (p = 0.7139). In situ hybridisation revealed a good correlation between gene expression levels and the above protein expression levels. Double IF identifies neutrophils and macrophages as the predominant sources of IL-1β. This study shows that IL-1β produced by macrophages and neutrophils and IL-1R3 are significantly overexpressed in SS, thereby indicating a potential pathogenic role for this cytokine and receptor in SS.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Klinikum der LMU München > Klinik und Poliklinik für Dermatologie und Allergologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0906-6705
• Sprache: Englisch