PMID- 27556858
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 46
DP  - 2016 Nov 15
TI  - Dendritic cell-derived nitric oxide inhibits the differentiation of effector 
      dendritic cells.
PG  - 74834-74845
LID - 10.18632/oncotarget.11361 [doi]
AB  - Dendritic cells (DCs) play a pivotal role in the development of effective immune 
      defense while avoiding detrimental inflammation and autoimmunity by regulating 
      the balance of adaptive immunity and immune tolerance. However, the mechanisms 
      that govern the effector and regulatory functions of DCs are incompletely 
      understood. Here, we show that DC-derived nitric oxide (NO) controls the balance 
      of effector and regulatory DC differentiation. Mice deficient in the NO-producing 
      enzyme inducible nitric oxide synthase (iNOS) harbored increased effector DCs 
      that produced interleukin-12, tumor necrosis factor (TNF) and IL-6 but normal 
      numbers of regulatory DCs that expressed IL-10 and programmed cell death-1 
      (PD-1). Furthermore, an iNOS-specific inhibitor selectively enhanced effector DC 
      differentiation, mimicking the effect of iNOS deficiency in mice. Conversely, an 
      NO donor significantly suppressed effector DC development. Furthermore, iNOS-/- 
      DCs supported enhanced T cell activation and proliferation. Finally iNOS-/- mice 
      infected with the enteric pathogen Citrobacter rodentium suffered more severe 
      intestinal inflammation with concomitant expansion of effector DCs in colon and 
      spleen. Collectively, our results demonstrate that DC-derived iNOS restrains 
      effector DC development, and offer the basis of therapeutic targeting of iNOS in 
      DCs to treat autoimmune and inflammatory diseases.
FAU - Si, Chuanping
AU  - Si C
AD  - Institute of Immunology and Molecular Medicine, Jining Medical College, Shandong 
      272067, China.
FAU - Zhang, Ruihua
AU  - Zhang R
AD  - Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Wu, Tianshu
AU  - Wu T
AD  - Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Lu, Geming
AU  - Lu G
AD  - Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Hu, Yuan
AU  - Hu Y
AD  - Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Institute of Immunology and Molecular Medicine, Jining Medical College, Shandong 
      272067, China.
FAU - Xu, Feihong
AU  - Xu F
AD  - Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Wei, Peter
AU  - Wei P
AD  - Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Chen, Kang
AU  - Chen K
AD  - Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI 
      48201, USA.
FAU - Tang, Hua
AU  - Tang H
AD  - Institute of Immunology, Taishan Medical University, Tai'an, Shandong 271000, 
      China.
FAU - Yeretssian, Garabet
AU  - Yeretssian G
AD  - Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
FAU - Xiong, Huabao
AU  - Xiong H
AD  - Institute of Immunology and Molecular Medicine, Jining Medical College, Shandong 
      272067, China.
AD  - Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount 
      Sinai, New York, NY 10029, USA.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Inflammasomes)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - *Cell Differentiation/genetics/immunology
MH  - Dendritic Cells/*cytology/immunology/*metabolism
MH  - Female
MH  - Gene Knockout Techniques
MH  - Immunity, Innate/genetics
MH  - Inflammasomes/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - T-Lymphocyte Subsets/immunology/metabolism
PMC - PMC5342705
OTO - NOTNLM
OT  - dendritic cell
OT  - iNOS
COIS- CONFLICTS OF INTEREST The authors declare that they have no competing interests.
EDAT- 2016/08/25 06:00
MHDA- 2018/02/27 06:00
PMCR- 2016/11/15
CRDT- 2016/08/25 06:00
PHST- 2016/04/14 00:00 [received]
PHST- 2016/07/27 00:00 [accepted]
PHST- 2016/08/25 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2016/08/25 06:00 [entrez]
PHST- 2016/11/15 00:00 [pmc-release]
AID - 11361 [pii]
AID - 10.18632/oncotarget.11361 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Nov 15;7(46):74834-74845. doi: 10.18632/oncotarget.11361.