# The Role of the Cysteamine Dioxygenase (ADO) Gene in Atopic Dermatitis

## TL;DR

This study shows that the ADO gene is linked to atopic dermatitis, affecting skin health and inflammation, and could be a target for new treatments.

## Contribution

The study identifies ADO as a key gene in atopic dermatitis pathogenesis through its effects on skin barrier and inflammation.

## Key findings

- ADO expression is higher in lesional skin of atopic dermatitis patients compared to non-lesional skin.
- ADO dysregulation in zebrafish leads to impaired epidermal development and increased inflammation.
- ADO influences proinflammatory cytokines, skin barrier markers, and reactive oxygen species in HaCaT cells.

## Abstract

Atopic dermatitis is a chronic inflammatory skin disorder influenced by genetic and environmental factors. A chromosome conformation capture study identified the cysteamine dioxygenase (ADO) gene as being associated with atopic dermatitis in differentiating keratinocytes. We aimed to evaluate the causal and pathophysiological roles of ADO in atopic dermatitis. This study utilized transcriptomic data and immunostaining techniques to analyse ADO expression. Human keratinocyte cell line (HaCat), and zebrafish models were employed to explore the functional role of ADO. RNA sequencing and immunostainings indicated higher ADO expression in lesional skin than in non-lesional skin in atopic dermatitis patients. Moreover, atopic dermatitis patients carrying the risk allele (C) exhibited increased levels of ADO in lesional skin. In vivo, zebrafish embryos with dysregulated ADO expression displayed impaired epidermal morphogenesis, particularly in their tails, along with increased neutrophil infiltration, indicating an inflammatory response. In vitro, alterations in ADO expression in HaCaT cells led to expression changes of proinflammatory cytokines and skin barrier markers. Further, both upregulation and downregulation of ADO were associated with enhanced reactive oxygen species production. These findings suggest that the ADO gene plays a critical role in maintaining skin homeostasis, and its dysregulation contributes to inflammation and compromised skin barrier function in the pathogenesis of atopic dermatitis.

Atopic dermatitis is a common chronic inflammatory skin disease with a strong genetic basis affecting millions of people worldwide. This study focuses on the ADO gene and reveals that abnormal ADO expression in atopic dermatitis patients impairs skin barrier function and triggers inflammation. We show that ADO influences epidermal differentiation, immune responses, and oxidative stress, postulating it as a key genetic factor in atopic dermatitis. These findings advance our understanding of atopic dermatitis causes and suggest ADO could serve as both a diagnostic marker and a target for future therapies.