Untargeted lipidomics studies in the course of dermatitis onset and progression
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ABSTRACT: We applied untargeted lipidomic analysis to the atopic dermatitis-like dermatitis model (Spade mice) to capture the comprehensive lipidome profile in the course of dermatitis onset and progression. Spade mice harbor a single amino acid mutation in Jak1 that causes hyperactivation, leading to Th2 dermatitis. Progressive dermatitis develops as desquamation and redness of the ears at approximately 8 weeks of age. At 10 weeks of age, serum IgE and IgG1 levels are increased, and Th2 cytokines, such as IL-4, IL-5, and IL-13, produced by CD4+ cells are upregulated, followed by elevated serum histamine levels at 12 weeks of age. Skin lesions manifest as epidermal hyperplasia at 8 weeks of age, while there are few morphological changes at 4 weeks of age. TEWL, the readout for barrier function, is significantly elevated in Spade mice at 4 weeks of age, suggesting that barrier defects had occurred before disease onset. WT and Spade skin tissues in P0, 4, 8, and 10 weeks of age were applied to untargeted lipidomics. Over 700 skin lipids including glycerophospholipids, ceramides, neutral lipids, and fatty acids were successfully annotated, and many of them were found to be significantly changed after dermatitis onset as determined by pruritus and erythema. Among them, the levels of Cer[NdS] containing very long-chain (C22 or more) fatty acids were significantly downregulated before AD onset.
ORGANISM(S): Mouse Mus Musculus
TISSUE(S): Skin
DISEASE(S): Dermatitis
SUBMITTER: Yudai Iino
PROVIDER: ST002195 | MetabolomicsWorkbench | Wed May 25 00:00:00 BST 2022
REPOSITORIES: MetabolomicsWorkbench
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