PMID- 37843504
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20240104
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 211
IP  - 11
DP  - 2023 Dec 1
TI  - Epigenetic Regulation of IL-23 by E3 Ligase FBXW7 in Dendritic Cells Is Critical 
      for Psoriasis-like Inflammation.
PG  - 1701-1713
LID - 10.4049/jimmunol.2300023 [doi]
AB  - Dendritic cells (DCs), a driver of psoriasis pathogenesis, produce IL-23 and 
      trigger IL-23/IL-17 cytokine axis activation. However, the mechanisms regulating 
      IL-23 induction remain unclear. In the current study, we found that mice with E3 
      ligase FBXW7 deficiency in DCs show reduced skin inflammation correlated with the 
      reduction of IL-23/IL-17 axis cytokines in the imiquimod-induced psoriasis model. 
      Fbxw7 deficiency results in decreased production of IL-23 in DCs. FBXW7 interacts 
      with the lysine N-methyltransferase suppressor of variegation 39 homolog 2 
      (SUV39H2), which catalyzes the trimethylation of histone H3 Lys9 (H3K9) during 
      transcription regulation. FBXW7 mediates the ubiquitination and degradation of 
      SUV39H2, thus decreasing H3K9m3 deposition on the Il23a promoter. The Suv39h2 
      knockout mice displayed exacerbated skin inflammation with the IL-23/IL-17 axis 
      overactivating in the psoriasis model. Taken together, our results indicate that 
      FBXW7 increases IL-23 expression in DCs by degrading SUV39H2, thereby aggravating 
      psoriasis-like inflammation. Inhibition of FBXW7 or the FBXW7/SUV39H2/IL-23 axis 
      may represent a novel therapeutic approach to psoriasis.
CI  - Copyright (c) 2023 by The American Association of Immunologists, Inc.
FAU - Song, Yinjing
AU  - Song Y
AD  - Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Zhao, Xiangtong
AU  - Zhao X
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Qu, Hao
AU  - Qu H
AUID- ORCID: 0000-0001-7633-7097
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital of Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Su, Yixin
AU  - Su Y
AUID- ORCID: 0000-0001-9917-0488
AD  - Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 
      China.
FAU - He, Rukun
AU  - He R
AUID- ORCID: 0000-0002-6346-4107
AD  - Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 
      China.
FAU - Chen, Luxia
AU  - Chen L
AD  - Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Fang, Lutong
AU  - Fang L
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Li, Jiaying
AU  - Li J
AUID- ORCID: 0009-0004-7042-8034
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Zou, Ziqi
AU  - Zou Z
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
FAU - He, Jia
AU  - He J
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
FAU - Li, Zilong
AU  - Li Z
AD  - Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing 
      Medical University, Nanjing, China.
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of 
      Pathophysiology, Nanjing Medical University, Nanjing, China.
FAU - Xu, Yaohan
AU  - Xu Y
AD  - Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Chen, Xin
AU  - Chen X
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Macau SAR, China.
FAU - Cheng, Hao
AU  - Cheng H
AD  - Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Xu, Yong
AU  - Xu Y
AD  - Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing 
      Medical University, Nanjing, China.
AD  - Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of 
      Pathophysiology, Nanjing Medical University, Nanjing, China.
AD  - Institute of Biomedical Research, Liaocheng University, Liaocheng, China.
FAU - Wang, Qingqing
AU  - Wang Q
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
AD  - Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
FAU - Lai, Lihua
AU  - Lai L
AD  - Department of Dermatology and Venereology, Sir Run Run Shaw Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
AD  - Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 
      China.
LA  - eng
GR  - 31870907/MOST | National Natural Science Foundation of China (NSFC)/
GR  - 81930041/MOST | National Natural Science Foundation of China (NSFC)/
GR  - 91842103/MOST | National Natural Science Foundation of China (NSFC)/
GR  - 81703135/MOST | National Natural Science Foundation of China (NSFC)/
GR  - 81771699/MOST | National Natural Science Foundation of China (NSFC)/
GR  - Z19H100001/MOST | NSFC | NSFC-Zhejiang Joint Fund | | Natural Science Foundation 
      of Zhejiang Province (ZJNSF)/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (F-Box-WD Repeat-Containing Protein 7)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-23)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - 0 (Il23a protein, mouse)
RN  - 0 (Fbxw7 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Dendritic Cells/metabolism
MH  - *Dermatitis/pathology
MH  - Disease Models, Animal
MH  - Epigenesis, Genetic
MH  - F-Box-WD Repeat-Containing Protein 7/genetics/metabolism
MH  - Inflammation/metabolism
MH  - Interleukin-17/metabolism
MH  - Interleukin-23/metabolism
MH  - *Psoriasis/pathology
MH  - Skin/pathology
MH  - Ubiquitin-Protein Ligases/genetics/metabolism
EDAT- 2023/10/16 12:42
MHDA- 2023/11/22 06:43
CRDT- 2023/10/16 10:43
PHST- 2023/01/12 00:00 [received]
PHST- 2023/08/11 00:00 [accepted]
PHST- 2023/11/22 06:43 [medline]
PHST- 2023/10/16 12:42 [pubmed]
PHST- 2023/10/16 10:43 [entrez]
AID - 266089 [pii]
AID - 10.4049/jimmunol.2300023 [doi]
PST - ppublish
SO  - J Immunol. 2023 Dec 1;211(11):1701-1713. doi: 10.4049/jimmunol.2300023.