Atopic dermatitis (AD) is a complex disease characterized by eczematous lesions over dry skin and local and systemic oxidative stress. Indeed, patients with AD display increased concentrations of oxidative stress biomarkers in the urine, blood, and saliva. Although the source of ROS in AD is uncertain, dysfunctional mitochondria might be involved in excessive oxidative stress in AD skin. In this study, we investigated oxidative stress in AD epidermis by using a mouse model of AD, i.e. flaky tail (ft/ft) mice, and primary keratinocytes and skin biopsies from AD patients. We found a dysregulated expression of genes involved in oxidative stress response in AD epidermis and keratinocytes. SOD2 and cytochrome c were increased, suggesting mitochondrial stress in AD epidermis. Furthermore, we observed a down-regulation of the glutathione system and of catalase in AD keratinocytes, which might lead to accumulation of hydrogen peroxide, mainly in mitochondria. Moreover, we showed an increase of malondialdehyde (MDA), 4-hydroxy-2-nonenal (4HNE), and oxidized phospholipids in AD epidermis. Nevertheless, despite low level of GPX4 and a high amount of lipid peroxides, ferroptosis and intrinsic apoptosis are not triggered in AD epidermis. Furthermore, MitoQ, but not NAC, ameliorates AD-like symptoms in ft/ft mice. Thus, this indicates that mitochondrial stress might be a significant source of ROS in AD keratinocytes and could contribute to AD pathogenesis.

ESDR331 - Mitochondrial stress contributes to atopic dermatitis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.