O15 Ceramides mediate the resolution of psoriasis-like skin inflammation

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ID: 318463
2026
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Abstract
Abstract Introduction and aims Psoriasis is a chronic inflammatory disease associated with keratinocyte hyperproliferation and immune cell accumulation in skin. However, much research has focused on the role of proteins in psoriasis and less on lipids, despite their prevalence in skin. Additionally, psoriasis often fails to resolve, and this is poorly understood. We hypothesize that bioactive lipids play critical roles in the resolution of skin inflammation and that targeting lipids therapeutically may be a novel approach to promote resolution. Methods Psoriasis-like skin inflammation was induced in female C57BL/6 mice by topically treating ear skin with 20 mg Aldara cream for 4 days. Treatment was then ceased and inflammation allowed to resolve. Immune cell numbers and ceramide profiles in ear skin were analysed at different timepoints by flow cytometry and liquid chromatography–mass spectrometry, respectively. The effect of ceramides on immune cell activity during resolution was determined by intraperitoneal injection of the ceramide synthase inhibitors FTY720 (3 mg kg−1) or Myriocin (1.3 mg kg−1) on days 5 and 7 after first Aldara treatment. Results Lipidomic profiling revealed significant changes to 32 nonhydroxy sphingosine ceramide species in inflammation or resolution compared with uninflamed mice. Interestingly, the species enriched during resolution were grouped by sphingosine base length and nonhydroxy acyl chain length. FTY720-treated mice, but not myriocin-treated, showed increased ear skin redness compared with those who were treated with vehicle. At day 8, flow cytometric analysis revealed significantly increased numbers of important immune cell populations; both treatments showed increased innate lymphoid cells, macrophages and γδ T-cell production of interleukin (IL)-17A in lymph node. This was also seen in skin from myriocin-treated mice, in addition to a significant increase in neutrophils. Conclusions Together, these results suggest that inhibition of ceramide synthesis in vivo increases inflammatory immune cell activity and inflammation severity, demonstrating a pro-resolution role for ceramides. Further investigation is warranted to determine the mechanisms by which ceramides mediate these effects.
Reference Key
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Authors Anna Hains, Megan Priestley, Alex Kendall, Anna Nicolaou, Tracy Hussell, Amy Saunders
Journal the british journal of dermatology
Year 2026
DOI
10.1093/bjd/ljag151.015
URL
https://doi.org/10.1093/bjd/ljag151.015
Keywords Keywords not found

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