PMID- 36271146
OWN - NLM
STAT- MEDLINE
DCOM- 20221116
LR  - 20221222
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 23
IP  - 11
DP  - 2022 Nov
TI  - IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies 
      IL-36R-mediated skin inflammation.
PG  - 1577-1587
LID - 10.1038/s41590-022-01339-3 [doi]
AB  - Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the 
      present study, we found that the RNA helicase DDX5 was downregulated in 
      keratinocytes from the inflammatory skin lesions in patients with atopic 
      dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of 
      Ddx5 (Ddx5(∆KC)) were more susceptible to cutaneous inflammation. Inhibition of 
      DDX5 expression in keratinocytes was induced by the cytokine interleukin (IL)-17D 
      through activation of the CD93-p38 MAPK-AKT-SMAD2/3 signaling pathway and led to 
      pre-messenger RNA splicing events that favored the production of membrane-bound, 
      intact IL-36 receptor (IL-36R) at the expense of soluble IL-36R (sIL-36R) and to 
      the selective amplification of IL-36R-mediated inflammatory responses and 
      cutaneous inflammation. Restoration of sIL-36R in Ddx5(∆KC) mice with 
      experimental atopic dermatitis or psoriasis suppressed skin inflammation and 
      alleviated the disease phenotypes. These findings indicate that IL-17D modulation 
      of DDX5 expression controls inflammation in keratinocytes during inflammatory 
      skin diseases.
CI  - (c) 2022. The Author(s).
FAU - Ni, Xinhui
AU  - Ni X
AUID- ORCID: 0000-0002-8786-3460
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Xu, Yi
AU  - Xu Y
AUID- ORCID: 0000-0001-9297-095X
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Wang, Wang
AU  - Wang W
AUID- ORCID: 0000-0002-5549-2706
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Kong, Baida
AU  - Kong B
AUID- ORCID: 0000-0001-6912-0463
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Ouyang, Jian
AU  - Ouyang J
AUID- ORCID: 0000-0002-7851-7064
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Chen, Jiwei
AU  - Chen J
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Yan, Man
AU  - Yan M
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Wu, Yawei
AU  - Wu Y
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Chen, Qi
AU  - Chen Q
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Wang, Xinxin
AU  - Wang X
AUID- ORCID: 0000-0002-7341-9780
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Li, Hongquan
AU  - Li H
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Gao, Xiaoguang
AU  - Gao X
AUID- ORCID: 0000-0002-8618-9128
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Guo, Hongquan
AU  - Guo H
AUID- ORCID: 0000-0002-1545-8087
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Cui, Lian
AU  - Cui L
AUID- ORCID: 0000-0003-0997-6424
AD  - Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, China.
FAU - Chen, Zeyu
AU  - Chen Z
AUID- ORCID: 0000-0001-6393-1986
AD  - Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, China.
FAU - Shi, Yuling
AU  - Shi Y
AD  - Department of Dermatology, Shanghai Tenth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, China.
AD  - Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 
      China.
FAU - Zhu, Ronghui
AU  - Zhu R
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Li, Wei
AU  - Li W
AUID- ORCID: 0000-0003-1186-8609
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Shi, Tieliu
AU  - Shi T
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China.
FAU - Wang, Lin-Fa
AU  - Wang LF
AD  - Emerging Infectious Diseases Program, Duke-NUS Graduate Medical School, 
      Singapore, Singapore.
AD  - Singhealth Duke-NUS Global Health Institute, Singapore, Singapore.
FAU - Huang, Jinling
AU  - Huang J
AD  - Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 
      China.
FAU - Dong, Chen
AU  - Dong C
AUID- ORCID: 0000-0002-0084-9130
AD  - Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 
      China.
AD  - Shanghai Immune Therapy Institute, Shanghai Jiaotong University School of 
      Medicine-affiliated Renji Hospital, Shanghai, China.
FAU - Lai, Yuping
AU  - Lai Y
AUID- ORCID: 0000-0001-7445-6738
AD  - Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai 
      Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal 
      University, Shanghai, China. yplai@bio.ecnu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221021
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Interleukin-27)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Interleukin-27/metabolism
MH  - *Dermatitis, Atopic/genetics/pathology
MH  - Keratinocytes/metabolism
MH  - Skin/pathology
MH  - *Psoriasis/genetics/pathology
MH  - Inflammation/metabolism
PMC - PMC9663298
COIS- Y.L., X.N., Y.X., W.W., Y.W., B.K. and X.G. have filed provisional patents 
      (202110117195.8 and 201910333393.0) disclosure based on the results in the paper. 
      The remaining authors declare no competing interests.
EDAT- 2022/10/22 06:00
MHDA- 2022/11/18 06:00
PMCR- 2022/10/21
CRDT- 2022/10/21 23:55
PHST- 2021/10/12 00:00 [received]
PHST- 2022/09/14 00:00 [accepted]
PHST- 2022/10/22 06:00 [pubmed]
PHST- 2022/11/18 06:00 [medline]
PHST- 2022/10/21 23:55 [entrez]
PHST- 2022/10/21 00:00 [pmc-release]
AID - 10.1038/s41590-022-01339-3 [pii]
AID - 1339 [pii]
AID - 10.1038/s41590-022-01339-3 [doi]
PST - ppublish
SO  - Nat Immunol. 2022 Nov;23(11):1577-1587. doi: 10.1038/s41590-022-01339-3. Epub 
      2022 Oct 21.