PMID- 31962236
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210110
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 23
IP  - 1
DP  - 2020 Jan 24
TI  - Spermidine Suppresses Inflammatory DC Function by Activating the FOXO3 Pathway 
      and Counteracts Autoimmunity.
PG  - 100807
LID - S2589-0042(19)30553-X [pii]
LID - 10.1016/j.isci.2019.100807 [doi]
LID - 100807
AB  - Dendritic cells (DCs) function is intimately linked to microenvironment and 
      metabolism. Type I interferons (IFNs) condition dendritic cells to respond to 
      weak self-signals, leading to autoimmunity. However, the metabolic adaption in 
      the process is unclear. Here, we identified spermidine as a critical metabolite 
      impacting the metabolic fitness of DC. First, dynamic metabolome screening 
      indicated that spermidine decreased during IFN priming and following TLR7 ligand 
      stimulation, accompanied by metabolic change from oxidative phosphorylation to 
      glycolysis. Second, spermidine supplement restrained the glycolysis and prevented 
      the overactivation of IFN-alpha primed DC both in vivo and in vitro. Third, mechanism 
      study uncovered that the activity of FOXO3 adapted to the metabolic change, 
      mediating the anti-inflammatory effect of spermidine. More importantly, addition 
      of spermidine in vivo greatly alleviated the development of psoriasis-like 
      symptom in mice. Thus, our studies revealed metabolic changes boosting DC 
      responses and identified spermidine as a potential therapeutic agent for 
      autoimmune diseases.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Li, Guanhua
AU  - Li G
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University 
      School of Medicine (SJTUSM), 145 Shan Dong Middle Road, Shanghai 200001, China.
FAU - Ding, Huihua
AU  - Ding H
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University 
      School of Medicine (SJTUSM), 145 Shan Dong Middle Road, Shanghai 200001, China.
FAU - Yu, Xiang
AU  - Yu X
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University 
      School of Medicine (SJTUSM), 145 Shan Dong Middle Road, Shanghai 200001, China.
FAU - Meng, Yao
AU  - Meng Y
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University 
      School of Medicine (SJTUSM), 145 Shan Dong Middle Road, Shanghai 200001, China.
FAU - Li, Jun
AU  - Li J
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University 
      School of Medicine (SJTUSM), 145 Shan Dong Middle Road, Shanghai 200001, China.
FAU - Guo, Qiang
AU  - Guo Q
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University 
      School of Medicine (SJTUSM), 145 Shan Dong Middle Road, Shanghai 200001, China.
FAU - Zhou, Haibo
AU  - Zhou H
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University 
      School of Medicine (SJTUSM), 145 Shan Dong Middle Road, Shanghai 200001, China; 
      Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen 518040, China. 
      Electronic address: hbzhou1984@gmail.com.
FAU - Shen, Nan
AU  - Shen N
AD  - Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University 
      School of Medicine (SJTUSM), 145 Shan Dong Middle Road, Shanghai 200001, China; 
      Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen 518040, China; Center 
      for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital 
      Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of 
      Cincinnati College of Medicine, Cincinnati, OH, USA; State Key Laboratory of 
      Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai 
      Jiao Tong University School of Medicine (SJTUSM), Shanghai 200032, China. 
      Electronic address: nanshensibs@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20191227
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC6971394
OTO - NOTNLM
OT  - Biological Sciences
OT  - Cell Biology
OT  - Immunology
OT  - Metabolomics
COIS- Declaration of Interests The authors declare no competing interests.
EDAT- 2020/01/22 06:00
MHDA- 2020/01/22 06:01
PMCR- 2019/12/27
CRDT- 2020/01/22 06:00
PHST- 2019/08/18 00:00 [received]
PHST- 2019/11/27 00:00 [revised]
PHST- 2019/12/23 00:00 [accepted]
PHST- 2020/01/22 06:00 [pubmed]
PHST- 2020/01/22 06:01 [medline]
PHST- 2020/01/22 06:00 [entrez]
PHST- 2019/12/27 00:00 [pmc-release]
AID - S2589-0042(19)30553-X [pii]
AID - 100807 [pii]
AID - 10.1016/j.isci.2019.100807 [doi]
PST - ppublish
SO  - iScience. 2020 Jan 24;23(1):100807. doi: 10.1016/j.isci.2019.100807. Epub 2019 
      Dec 27.