Atopic dermatitis (AD) affects up to 20% of children worldwide. It is the most common inflammatory skin disease, characterized by pruritus, eczema and abnormal IgE responses to environmental substances. The disease has an increasing medical and socio-economic impact on affected patients and their families and health care systems. Multiple factors likely contribute to the pathogenesis of atopic dermatitis, but recent work has focused on abnormalities of the epidermis, a critical barrier between the environment and host innate and adaptive immune responses.
The mechanisms that regulate epidermal barrier function are incompletely understood. Researchers from GiGa (ULg), have found that deletion of the gene RABGEF1 in keratinocytes, severely impairs epidermal barrier function in mice and induces an allergic cutaneous and systemic phenotype. RAGBEF1 is responsible to dampen activation of IL-1R– and MYD88-dependent pathways in epidermal keratinocytes. Abberant regulation of the latter pathways results in abnormal expression of structural proteins that contribute to skin barrier function. The GiGa research team reported that interrupting MYD88 or IL-R1 signaling restored skin homeostasis and prevented development of skin inflammation. Therefore RAGBEF1 and its downregulated pathway might represent a potential therapeutic target to treat atopic dermatitis.
This study was published in The Journal of Clinical Investigation.
Reference
Marichal, Thomas, et al. “Guanine nucleotide exchange factor RABGEF1 regulates keratinocyte-intrinsic signaling to maintain skin homeostasis.” The Journal of Clinical Investigation 126.12 (2016).
