Lipid abnormalities in atopic skin are driven by type 2 cytokines

• DOI: 10.1172/jci.insight.98006
• Publication Date: 2018-02-21T16:00:58Z
• Authors: Evgeny Berdyshev; Elena Goleva; Irina Bronova; Nathan Dyjack; Cydney Rios; John Jung; Patricia Taylor; Mingeum Jeong; Clifton F. Hall; Brittany N. Richers; Kathryn A. Norquest; Tao Zheng; Max A. Seibold; Donald Y.M. Leung
• Keywords: Sphingolipid

Lipids in the stratum corneum of atopic dermatitis (AD) patients differ substantially composition from healthy subjects. We hypothesized that hyperactivated type 2 immune response alters AD skin lipid metabolism. have analyzed lipids nonlesional and lesional subjects IL-13 skin-specific Tg mice. also directly examined effects IL-4/IL-13 on human keratinocytes vitro. Mass spectrometric analysis mice revealed an increased proportion short-chain (N-14:0 to N-24:0) NS ceramides, sphingomyelins, 14:0-22:0 lysophosphatidylcholines (14:0-22:0 LPC) with a simultaneous decline corresponding long-chain species (N-26:0 N-32:0 sphingolipids 24:0-30:0 when compared controls. An increase LPC was observed skin. Similar changes were IL-4/IL-13-driven responses Ca2+-differentiated vitro, all being blocked by STAT6 silencing siRNA. RNA sequencing performed as identified decreased expression fatty acid elongases ELOVL3 ELOVL6 contributed lipids. inhibited keratinocyte cultures STAT6-dependent manner. Downregulation ELOVL3/ELOVL6 siRNA acids globally sphingolipids. Thus, our data strongly support pathogenic role activation