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Lipids in the stratum corneum of atopic dermatitis (AD) patients differ substantially in composition from healthy subjects. We hypothesized that hyperactivated type 2 immune response alters AD skin lipid metabolism. We have analyzed stratum corneum lipids from nonlesional and lesional skin of AD subjects and IL-13 skin-specific Tg mice. We also directly examined the effects of IL-4/IL-13 on human keratinocytes in vitro. Mass spectrometric analysis of lesional stratum corneum from AD subjects and IL-13 Tg mice revealed an increased proportion of short-chain (N-14: 0 to N-24: 0) NS ceramides, sphingomyelins, and 14: 0–22: 0 lysophosphatidylcholines (14: 0–22: 0 LPC) with a simultaneous decline in the proportion of corresponding long-chain species (N-26: 0 to N-32: 0 sphingolipids and 24: 0–30: 0 LPC) when compared with healthy controls. An increase in short-chain LPC species was also observed in …