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The following is a summary of “A role for Arginase in skin epithelial differentiation and anti-microbial peptide production,” published in the February 2025 issue of British Journal of Dermatology by Szondi et al. 

Arginase 1 (ARG1), an enzyme expressed by keratinocytes and involved in skin barrier function, was investigated in relation to atopic dermatitis (AD), a condition characterized by impaired barrier function due to altered keratinocyte differentiation and increased infection susceptibility.  

Researchers conducted a retrospective study to examine the role of ARG1 in keratinocyte differentiation and antimicrobial responses.  

They utilized in vitro 2D differentiation assays with ARG1 knockdown or ARG1-inhibited keratinocytes to examine its role in keratinocyte differentiation and barrier formation and the ARG1 expression was also evaluated in an ex vivo AD model.  

The results showed that ARG1 was highly expressed in the apical layers of human skin, aligning with increased ARG1 levels in late-differentiated keratinocytes while, ARG1 expression was reduced in an ex vivo AD model compared to controls, indicating clinical relevance. Inhibiting ARG1 in keratinocytes significantly decreased late differentiation markers Filaggrin (FLG), Involucrin (IVL), and Loricrin (LOR), along with antimicrobial peptides (AMPs) such as Lipocalin 2 (LCN2), Kallikreins (KLKs), and Small Proline Rich Proteins (SPRRs). As part of the urea cycle, ARG1 converts L-arginine into L-ornithine and urea, with L-ornithine further metabolized to produce putrescine (Put). Supplementation with ARG1 products, Put, and urea restored late keratinocyte differentiation and AMP expression in ARG1-deficient cells.  

Investigators concluded that ARG1 activity played a major role in keratinocyte differentiation and AMP production, and while ARG1 was downregulated in AD, its downstream products, Put, and urea, could rescue it in cell systems, suggesting potential therapeutic manipulation of the ARG1 pathway for skin conditions like AD. 

Source: academic.oup.com/bjd/advance-article/doi/10.1093/bjd/ljaf057/8015494