Skin imaging mass spectrometry of controls versus atopic dermatitis patients with and without STAT3 mutations

Defects in lipid metabolism have been associated with inflammatory skin diseases such as atopic dermatitis (AD). The goal of this study was to characterize the biosynthetic pathways activated during epidermal repair using MALDI imaging mass spectrometry (IMS). Keratinocyte models confirmed the importance of glycerophospholipids, glycosphingolipids, and sialic acid in wound closure. In skin biopsies of healing tissue taken from healthy volunteers, phospholipids known to play critical roles in membrane repair and cell signaling were upregulated. Compared to controls, patients with AD had defects in lipid metabolism, including lysophosphatidylcholine moieties which provided modest clinical improvement in a mouse model of AD. Appling this workflow to patients with eczematous phenotypes due to dominant negative mutations identified metabolic disruption of thiamine and phosphatidylinositol metabolism. Overall, the results indicate MALDI imaging can be used to characterize changes in lipid metabolism during wound healing and may indicate an underappreciated role of lysophosphatidylcholine during tissue repair.