P44 Upregulation of beta defensin in human epidermal organoids treated with combinations of IL17 and IL23

Abstract Psoriasis is a chronic inflammatory skin disease characterized by the hyperproliferation of keratinocytes and an aberrant immune response. The pro-inflammatory cytokines IL-17 (a, e, f) and IL-23 play crucial roles in the pathogenesis of psoriasis. Human epidermal organoids (HEOs) are an in vitro model that recapitulates the epidermis and a useful tool for studying epidermal biology and disease mechanisms. HEOs were treated with various combinations of cytokines, including IL-17a, IL-17e, IL-17f, and IL-23. Following treatment, quantitative PCR (qPCR) and immunohistochemistry (IHC) were performed to assess the expression levels of beta-defensin, an antimicrobial peptide implicated in psoriasis. The qPCR analysis revealed significant upregulation of beta defensin in HEOs treated with the following cytokine combinations: IL-17a alone, IL-17f alone, IL-17a+e, IL-17a+f, IL-17a+IL-23, IL-17a+e+f, IL-17a+e+IL-23, IL-17a+f+IL-23, and IL-17a+e+f+IL-23. Conditions lacking IL-17a exhibited markedly lower beta-defensin expression, indicating the critical role of IL-17a in this process. However, IL-17f alone induced a moderate upregulation of beta-defensin. The study demonstrates that IL-17a is a pivotal cytokine in inducing beta-defensin expression in HEOs, with IL-17f also contributing to a lesser extent. The significant upregulation of beta-defensin in response to these cytokines suggests a key role for beta-defensin in the pathophysiology of psoriasis, potentially linking antimicrobial peptide activity to disease severity and progression.