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PXD021379 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDDX5-sIL-36R in keratinocytes controls skin inflammation
DescriptionThe DEAD-box (DDX) proteins function in diverse cellular processes including RNA alternative splicing, and are linked to immune-mediated diseases. However, little is known about the roles of DDXs in skin inflammatory diseases. Here, we show that DDX5, one of the founding members of the DDX RNA helicase family, controls skin inflammation and participates in the pathogenesis of psoriasis via regulating IL-36R pre-mRNA splicing. We found that both mRNA and protein of DDX5 are decreased in lesional skin from patients with psoriasis and psoriasis-like mice, and that mice with keratinocyte-specific ablation of DDX5 spontaneously develop psoriasis-like phenotypes. Mechanistically, DDX5 complexes with serine/arginine-rich splicing factor 1(SRSF1) to typically regulate IL-36R pre-mRNA splicing in keratinocytes, which generates mRNAs encoding full-length IL-36R and a previously unknown soluble form of IL-36R (sIL-36R). sIL-36R controls IL-36/IL-36R signaling by competing with IL-36R for IL-36γ ligation. The reduction or deficiency of DDX5 leads to IL-36R pre-mRNA splicing preferring to the generation of IL-36R but not sIL-36R, thereby selectively amplifying inflammatory responses of keratinocytes to IL-36γ and then aggravating cutaneous inflammation in psoriasis. Genetic restoration or intradermal administration of sIL-36R in psoriasis-like mice suppresses IL-36R signaling and alleviates the disease phenotype of psoriasis. Altogether, these data reveal a pathogenic role of DDX5 during psoriasis, and provide mechanistic insights into the regulation of IL-36R splicing and its impact on psoriasis development.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJiwei Chen
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-09 07:58:00ID requested
12021-09-06 01:10:29announced
22023-03-01 22:53:03announced2023-03-02: Update publication information.
Publication List
Ni X, Xu Y, Wang W, Kong B, Ouyang J, Chen J, Yan M, Wu Y, Chen Q, Wang X, Li H, Gao X, Guo H, Cui L, Chen Z, Shi Y, Zhu R, Li W, Shi T, Wang LF, Huang J, Dong C, Lai Y, IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation. Nat Immunol, 23(11):1577-1587(2022) [pubmed]
Keyword List
submitter keyword: DDX5, IL36, inflammation, psoriasis
Contact List
Yuping Lai
contact affiliationEast China Normal University
contact emailyplai@bio.ecnu.edu.cn
lab head
Jiwei Chen
contact affiliationEast China Normal University
contact emailchenjiwei@bio.ecnu.edu.cn
dataset submitter
Full Dataset Link List
iProX dataset URI