PMID- 30393085
OWN - NLM
STAT- MEDLINE
DCOM- 20200225
LR  - 20200225
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 139
IP  - 3
DP  - 2019 Mar
TI  - Production of Extracellular Adenosine by CD73(+) Dendritic Cells Is Crucial for 
      Induction of Tolerance in Contact Hypersensitivity Reactions.
PG  - 541-551
LID - S0022-202X(18)32708-8 [pii]
LID - 10.1016/j.jid.2018.10.016 [doi]
AB  - Dendritic cells (DCs) express the ecto-5'-nucleotidase CD73 that generates 
      immunosuppressive adenosine (Ado) by dephosphorylation of extracellular Ado 
      monophosphate and diphosphate. To investigate whether CD73-derived Ado has 
      immune-suppressive activity, 2,4-dinitrothiocyanobenzene (DNTB) was applied to 
      skin of wild-type (WT) or CD73-deficient (CD73(-/-)) mice, followed by 
      sensitization and challenge with 2,4-dinitrofluorobenzene. In this model, we show 
      the induction of tolerance by DNTB against 2,4-dinitrofluorobenzene only in WT 
      but not in CD73(-/-) mice. Analysis of skin DCs showed increased expression of 
      CD73 after application of DNTB in WT mice. That was accompanied by elevated 
      concentrations of extracellular Ado in the lymph node. Moreover, T cells 
      expressed markers for anergy, namely EGR2 and NDRG1 in DNTB-treated WT mice and 
      they exhibited impaired proliferation upon ex vivo re-stimulation. Similarly, 
      in vitro we observed that Ado-producing WT DCs, but not CD73(-/-) DCs, rendered 
      transgenic T cells from OTII mice (OTII T cells) hyporeactive, decreased their 
      T-cell costimulatory signaling, and induced up-regulation of EGR2 and NDRG1. 
      Thus, these data show that expression of CD73 by DCs, which triggers elevated 
      levels of extracellular Ado, is a crucial mechanism for the induction of anergic 
      T cells and tolerance.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Silva-Vilches, Cinthia
AU  - Silva-Vilches C
AD  - Department of Dermatology, Ruprecht-Karls-University Heidelberg, Heidelberg, 
      Germany.
FAU - Ring, Sabine
AU  - Ring S
AD  - Department of Dermatology, Ruprecht-Karls-University Heidelberg, Heidelberg, 
      Germany.
FAU - Schrader, Jurgen
AU  - Schrader J
AD  - Institute for Molecular Cardiology, Heinrich-Heine-University Dusseldorf, 
      Dusseldorf, Germany.
FAU - Clausen, Bjorn E
AU  - Clausen BE
AD  - Institute for Molecular Medicine, University Medical Center of the Johannes 
      Gutenberg-University Mainz, Mainz, Germany.
FAU - Probst, Hans-Christian
AU  - Probst HC
AD  - Institute for Immunology, University Medical Center of the Johannes 
      Gutenberg-University Mainz, Mainz, Germany.
FAU - Melchior, Felix
AU  - Melchior F
AD  - Institute for Immunology, University Medical Center of the Johannes 
      Gutenberg-University Mainz, Mainz, Germany.
FAU - Schild, Hansjorg
AU  - Schild H
AD  - Institute for Immunology, University Medical Center of the Johannes 
      Gutenberg-University Mainz, Mainz, Germany.
FAU - Enk, Alexander
AU  - Enk A
AD  - Department of Dermatology, Ruprecht-Karls-University Heidelberg, Heidelberg, 
      Germany.
FAU - Mahnke, Karsten
AU  - Mahnke K
AD  - Department of Dermatology, Ruprecht-Karls-University Heidelberg, Heidelberg, 
      Germany. Electronic address: karsten.mahnke@med.uni-heidelberg.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181028
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (GPI-Linked Proteins)
RN  - EC 3.1.3.5 (5'-Nucleotidase)
RN  - EC 3.1.3.5 (NT5E protein, human)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - 5'-Nucleotidase/*immunology
MH  - Adenosine/*metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology
MH  - Dermatitis, Allergic Contact/*immunology/pathology
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - GPI-Linked Proteins/immunology
MH  - Immune Tolerance/*immunology/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Random Allocation
MH  - Real-Time Polymerase Chain Reaction/methods
MH  - T-Lymphocytes, Regulatory/*immunology/metabolism
EDAT- 2018/11/06 06:00
MHDA- 2020/02/26 06:00
CRDT- 2018/11/06 06:00
PHST- 2018/06/28 00:00 [received]
PHST- 2018/10/02 00:00 [revised]
PHST- 2018/10/15 00:00 [accepted]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2020/02/26 06:00 [medline]
PHST- 2018/11/06 06:00 [entrez]
AID - S0022-202X(18)32708-8 [pii]
AID - 10.1016/j.jid.2018.10.016 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2019 Mar;139(3):541-551. doi: 10.1016/j.jid.2018.10.016. Epub 
      2018 Oct 28.