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Lipidomic profiling reveals metabolic signatures in psoriatic skin lesions.

Authors :
Liu, Panpan
Hou, Guixue
Kuang, Yehong
Li, Lei
Chen, Chao
Yan, Bei
Zhu, Wu
Li, Jie
Chen, Mingliang
Su, Juan
Lin, Liang
Chen, Xiang
Peng, Cong
Source :
Clinical Immunology. Jan2023, Vol. 246, pN.PAG-N.PAG. 1p.
Publication Year :
2023

Abstract

Psoriasis is a chronic immune-mediated inflammatory disease. Lipids play an important role in regulating the inflammatory response. However, the alteration of lipids involved in psoriasis particular in skin lesions remain unclear. Here, we performed the lipidomics to investigate lipid profiling in the skin lesions of the imiquimod-induced psoriasis-like dermatitis and psoriasis patients. The findings showed that ceramides phosphate (CerP) and ceramides were enriched in psoriatic lesions compared with controls from both psoriasis patients and psoriasis-like mouse model. Psoriasis patients were classified into two subtypes, the CC1 and CC2, by consensus clustering of these lipid signatures. The CC1 was characterized by the higher levels of CerP, uric acid, and more severe psoriasis, compared with CC2 subtype. Interestingly, ceramide-1-phosphate (C1P), dramatically enriched in CC1 subtype, facilitated imiquimod-induced psoriasis-like inflammatory responses. Mechanistically, C1P induced the expression of inflammatory factors and activated DNA replication and cell cycle signaling pathways in the primary keratinocytes. Inhibiting the production of C1P with ceramide kinase inhibitor effectively alleviated the imiquimod-induced psoriasis-like inflammation. Taken together, we described the landscape of lipids alteration and established lipids classification based on pattern of abundance of lipids in psoriatic skin lesions. Suppression of C1P pathway is a novel potential strategy for psoriasis treatment. [Display omitted] • Ceramides phosphate (CerP) and ceramides were enriched in psoriatic lesions compared with controls • The psoriasis was classified into two subtypes by consensus clustering of lipid signatures • One of subtypes was characterized by the higher levels of CerP and more severe psoriasis • Ceramide-1-phosphate (C1P) facilitated psoriasis like dermatitis • Suppression of C1P pathway effectively alleviated pathogenesis of psoriasis [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15216616
Volume :
246
Database :
Academic Search Index
Journal :
Clinical Immunology
Publication Type :
Academic Journal
Accession number :
161281371
Full Text :
https://doi.org/10.1016/j.clim.2022.109212