331 UBE2L3 reduces interleukin-1β secretion in epidermal keratinocytes and deficiency of UBE2L3 results in spontaneous psoriasis-like dermatitis
نویسندگان
چکیده
Proinflammatory cytokines, such as interleukin-1 beta (IL-1β), are important mediators of psoriasis. Ubiquitin conjugating enzyme E2 L3 (UBE2L3), an enzyme, is thought to be indirect target IL-1β secretion by binding ubiquitin ligases (E3s) tripartite motif-containing protein 21 (TRIM21). However, its role in the psoriasis remains unknown. In this study, we found that UBE2L3 expression was decreased psoriatic epidermis, while cysteine-aspartic acid protease 1 (Casp1) and signaling were strongly activated. Treatment with a Casp1 inhibitor reversed decrease level UBE2L3. addition, overexpression reduced TRIM21, STAT3 pathway activity precursor (pro-IL-1β). Consistently, silencing enhanced TRIM21 expression, activation pro-IL-1β production. Besides, imiquimod-induced mouse model, reduction localized ameliorated psoriasis-like lesions, mature levels epidermis. Bulk-RNA-seq, single cell sequencing multi-color flow cytometry major experiments performed identify central types function on Ube2l3 conditional knockout models, which epidermal deficiency results spontaneous dermatitis through γδT derived IL-17/IL-23 axis. Thus, may protective biomarker regulates IL-1β, IL-17 inhibits epidermis
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.336