Epidermal Fatty Acid‒Binding Protein Mediates Depilatory-Induced Acute Skin Inflammation

• DOI: 10.1016/j.jid.2021.11.040
• Publication Date: 2021-12-21T01:06:29Z
• Authors: Di Yin; Jiaqing Hao; Rong Jin; Yanmei Yi; Sobha R. Bodduluri; Yuan Hua; Ajay Anand; Yibin Deng; Bodduluri Haribabu; Nejat K. Egilmez; Edward R. Sauter; Bing Li
• Keywords: Inflammation; Keratinocytes; 0301 basic medicine; Mice; Phospholipases A2; 03 medical and health sciences; Peroxisome Proliferator-Activated Receptors; Animals; Humans; Dermatitis; Fatty Acid-Binding Proteins; Neoplasm Proteins

Depilatory creams are widely used to remove unwanted body hair, but people with sensitive skin are subject to depilatory-induced skin burn/inflammation. It remains unknown what makes their skin more sensitive than others. In this study, we show that epidermal fatty acid‒binding protein (E-FABP) expressed in the skin plays a critical role in promoting depilatory-induced acute skin inflammation in mouse models. Although a depilatory cream removed hair by breaking down keratin disulfide bonds, it activated cytosolic phospholipase A2, leading to activation of the arachidonic acid/E-FABP/peroxisome proliferator-activated receptor β signaling pathway in keratinocytes. Specifically, peroxisome proliferator-activated receptor β activation induced downstream targets (e.g., cyclooxygenase 2) and chemokine (e.g., CXCL1) production, which systemically mobilized neutrophils and recruited them to localize in the skin for acute inflammatory responses. Importantly, E-FABP deletion by CRISPR-Cas9 reduced cytosolic phospholipase A2/peroxisome proliferator-activated receptor β activation in keratinocytes, and genetic deletion of E-FABP protected mice from depilatory cream-induced neutrophil recruitment and skin inflammation. Our findings suggest E-FABP as a molecular sensor for sensitive skin by triggering depilatory-induced, lipid-mediated skin inflammatory responses.