Phospholipase A in skin biology: new insights from gene-manipulated mice and lipidomics.

The skin represents one of the tissues that are most profoundly influenced by alterations in the quality of lipids (lipoquality). Lipids not only constitute cellular membranes, but also serve as bioactive lipid mediators and essential components of the skin barrier. Phospholipase A (PLA) enzymes supply fatty acids and lysophospholipids from membrane phospholipids, thereby variably affecting cutaneous homeostasis. Accordingly, perturbation of particular PLA-driven lipid pathways can be linked to various forms of skin disease. In this review article, we highlight the roles of several PLA subtypes in cutaneous pathophysiology, as revealed by transgenic/knockout studies in combination with comprehensive lipidomics. We focus mainly on secreted PLA group IIF (sPLA-IIF), which is associated with epidermal hyperplasia through mobilization of a unique lipid metabolite. We also address the distinct roles of sPLA-IIE in hair follicles and sPLA-IID in lymphoid immune cells that secondarily affect cutaneous inflammation, and provide some insights into species differences in sPLAs. Additionally, we briefly overview the patatin-like phospholipase PNPLA1, which belongs to the Ca-independent PLA (iPLA) family, as a key regulator of skin barrier function through catalysis of a unique non-PLA reaction. These knowledges on lipid metabolism driven by various PLA subtypes will open novel opportunities for translated studies toward diagnosis and therapy of human skin diseases.