Dysregulated ceramide metabolism in mouse progressive dermatitis resulting from constitutive activation of Jak1

Yudai Iino, Tatsuro Naganuma, Makoto Arita

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Coordinated lipid metabolism contributes to maintaining skin homeostasis by regulating skin barrier formation, immune reactions, thermogenesis, and perception. Several reports have documented the changes in lipid composition in dermatitis, including in atopic dermatitis (AD); however, the specific mechanism by which these lipid profiles are altered during AD pathogenesis remains unknown. Here, we performed untargeted and targeted lipidomic analyses of an AD-like dermatitis model resulting from constitutive activation of Janus kinase 1 (Spade mice) to capture the comprehensive lipidome profile during dermatitis onset and progression. We successfully annotated over 700 skin lipids, including glycerophospholipids, ceramides, neutral lipids, and fatty acids, many of which were found to be present at significantly changed levels after dermatitis onset, as determined by the pruritus and erythema. Among them, we found the levels of ceramides composed of nonhydroxy fatty acid and dihydrosphingosine containing very long-chain (C22 or more) fatty acids were significantly downregulated before AD onset. Furthermore, in vitro enzyme assays using the skin of Spade mice demonstrated the enhancement of ceramide desaturation. Finally, we revealed topical application of ceramides composed of nonhydroxy fatty acid and dihydrosphingosine before AD onset effectively ameliorated the progression of AD symptoms in Spade mice. Our results suggest that the disruption in epidermal ceramide composition is caused by boosting ceramide desaturation in the initiation phase of AD, which regulates AD pathogenesis.

Original languageEnglish
Article number100329
JournalJournal of lipid research
Volume64
Issue number2
DOIs
Publication statusPublished - 2023 Feb

Keywords

  • Atopic dermatitis
  • Cer [NDS]
  • LC-MS/MS
  • ceramide desaturation
  • ceramides
  • lipidomics
  • lipids
  • skin
  • sphingolipids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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