{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:29:05Z","timestamp":1792985345534,"version":"4.5.0"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"4","funder":[{"name":"NIH\/NIAMS","award":["R01 AR41256"],"award-info":[{"award-number":["R01 AR41256"]}]},{"name":"NIH\/NIAID","award":["U19 AI117673"],"award-info":[{"award-number":["U19 AI117673"]}]},{"name":"NIH\/NCRR","award":["UL1 RR025780"],"award-info":[{"award-number":["UL1 RR025780"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,22]]},"abstract":"<jats:p>\n                    Lipids in the\n                    <jats:italic>stratum corneum<\/jats:italic>\n                    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\n                    <jats:italic>stratum corneum<\/jats:italic>\n                    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\n                    <jats:italic>stratum corneum<\/jats:italic>\n                    from AD subjects and IL-13 Tg mice revealed an increased proportion of short-chain (\n                    <jats:italic>N<\/jats:italic>\n                    -14:0 to\n                    <jats:italic>N<\/jats:italic>\n                    -24:0) NS ceramides, sphingomyelins, and 14:0\u201322:0 lysophosphatidylcholines (14:0\u201322:0 LPC) with a simultaneous decline in the proportion of corresponding long-chain species (\n                    <jats:italic>N<\/jats:italic>\n                    -26:0 to\n                    <jats:italic>N<\/jats:italic>\n                    -32:0 sphingolipids and 24:0\u201330:0 LPC) when compared with healthy controls. An increase in short-chain LPC species was also observed in nonlesional AD skin. Similar changes were observed in IL-4\/IL-13\u2013driven responses in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -differentiated human keratinocytes in vitro\n                    <jats:italic>,<\/jats:italic>\n                    all being blocked by STAT6 silencing with siRNA. RNA sequencing analysis performed on\n                    <jats:italic>stratum corneum<\/jats:italic>\n                    of AD as compared with healthy subjects identified decreased expression of fatty acid elongases ELOVL3 and ELOVL6 that contributed to observed changes in atopic skin lipids. IL-4\/IL-13 also inhibited ELOVL3 and ELOVL6 expression in keratinocyte cultures in a STAT6-dependent manner. Downregulation of ELOVL3\/ELOVL6 expression in keratinocytes by siRNA decreased the proportion of long-chain fatty acids globally and in sphingolipids. Thus, our data strongly support the pathogenic role of type 2 immune activation in AD skin lipid metabolism.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.98006","type":"journal-article","created":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T11:00:58Z","timestamp":1519210858000},"source":"Crossref","is-referenced-by-count":267,"title":["Lipid abnormalities in atopic skin are driven by type 2 cytokines"],"prefix":"10.1172","volume":"3","author":[{"given":"Evgeny","family":"Berdyshev","sequence":"first","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Goleva","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Bronova","sequence":"additional","affiliation":[{"name":"Department of 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