Acid ceramidase overactivity drives ceramide loss, leading to atopic dry skin and Th2-skewed immune polarization - PubMed
5 hours ago
- #Th2 Immune Response
- #Ceramide Deficiency
- #Atopic Dermatitis
- Acid ceramidase overactivity leads to ceramide loss in the stratum corneum (SC), contributing to atopic dermatitis (AD).
- Transgenic (Tg) mice with overexpressed mutant acid ceramidase developed scaly, noninflammatory skin with impaired barrier and water-holding capacity.
- Tg mice showed reduced SC ceramide levels, increased epidermal innervation, and decreased semaphorin 3a protein levels.
- AD-associated biomarkers were altered in Tg mice, including increased Il10, Il17a, S100a proteins, and decreased Cxcl10, Ifng, Il2, Il13, Il33, Sema3a, and Tlr9.
- Topical mite antigen application induced allergic responses in Tg mice, marked by eosinophil infiltration and elevated serum IgE levels.
- Allergen-challenged Tg mice exhibited increased expression of inflammatory mediators like Ccl17, Ccl22, Ccl26, Ccl27, Il3, Il13, Il22, and Il33.
- The study establishes Tg mice as a relevant AD model, highlighting ceramide-dependent mechanisms in AD pathogenesis.