CD73 contributes to anti-inflammatory properties of afferent lymphatic endothelial cells in humans and mice.
5'-Nucleotidase
/ antagonists & inhibitors
Animals
Antibodies, Blocking
/ administration & dosage
Cell Differentiation
/ immunology
Cells, Cultured
Child
Child, Preschool
Dendritic Cells
/ immunology
Endothelial Cells
/ enzymology
Female
GPI-Linked Proteins
/ antagonists & inhibitors
Gene Knockout Techniques
Gene Silencing
Humans
Inflammation
/ immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Up-Regulation
CD73
dendritic cells
lymphatic endothelial cells
siRNA
vascular biology
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
09
10
2019
revised:
23
07
2020
accepted:
22
09
2020
pubmed:
25
9
2020
medline:
23
4
2021
entrez:
24
9
2020
Statut:
ppublish
Résumé
CD73 is an important ectoenzyme responsible for the production of extracellular adenosine. It is involved in regulating inflammatory responses and cell migration and is overexpressed in various cancers. The functions of CD73 in blood endothelial cells are understood in detail, but its role on afferent lymphatics remains unknown. Moreover, anti-CD73 antibodies are now used in multiple clinical cancer trials, but their effects on different endothelial cell types have not been studied. This study reveals that a previously unknown role of CD73 on afferent lymphatics is to dampen immune responses. Knocking it out or suppressing it by siRNA leads to the upregulation of inflammation-associated genes on lymphatic endothelial cells and a more pro-inflammatory phenotype of interacting dendritic cells in vitro and in vivo. In striking contrast, anti-CD73 antibodies had only negligible effects on the gene expression of lymphatic- and blood-endothelial cells. Our data thus reveal new functions of lymphatic CD73 and indicate a low likelihood of endothelial cell-related adverse effects by CD73 targeting therapeutic antibodies.
Identifiants
pubmed: 32970335
doi: 10.1002/eji.201948432
pmc: PMC7821194
doi:
Substances chimiques
Antibodies, Blocking
0
GPI-Linked Proteins
0
5'-Nucleotidase
EC 3.1.3.5
NT5E protein, human
EC 3.1.3.5
Nt5e protein, mouse
EC 3.1.3.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
231-246Informations de copyright
© 2020 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
Références
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2588-92
pubmed: 8637918
Cell Rep. 2019 May 21;27(8):2411-2425.e9
pubmed: 31116985
N Engl J Med. 2012 Dec 13;367(24):2322-33
pubmed: 23234515
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Eur J Immunol. 2019 Oct;49(10):1457-1973
pubmed: 31633216
Front Immunol. 2014 Apr 01;5:131
pubmed: 24744755
Pharmacol Rev. 2011 Mar;63(1):1-34
pubmed: 21303899
J Thorac Oncol. 2011 Nov;6(11):1833-40
pubmed: 22011649
Eur J Immunol. 2015 Feb;45(2):371-5
pubmed: 25641680
J Immunol. 2009 Apr 15;182(8):4616-23
pubmed: 19342636
J Cell Biol. 1997 Jan 27;136(2):421-31
pubmed: 9015312
Blood. 2008 Sep 1;112(5):1822-31
pubmed: 18559975
Bioinformatics. 2008 Jun 15;24(12):1461-2
pubmed: 18441000
J Immunol. 2013 Oct 15;191(8):4165-73
pubmed: 24043904
Eur J Immunol. 2015 Feb;45(2):562-73
pubmed: 25402681
Circulation. 2006 May 2;113(17):2120-7
pubmed: 16636171
Nature. 1998 Mar 19;392(6673):245-52
pubmed: 9521319
Bioinformatics. 2010 Nov 15;26(22):2927-8
pubmed: 20926419
J Invest Dermatol. 1989 Nov;93(5):600-9
pubmed: 2529318
Oncogene. 2010 Sep 30;29(39):5346-58
pubmed: 20661219
Blood. 2011 Apr 21;117(16):4387-93
pubmed: 21346249
Am J Transl Res. 2014 Jan 15;6(2):129-39
pubmed: 24489992
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Genome Biol. 2014;15(12):550
pubmed: 25516281
BMC Genomics. 2017 Aug 17;18(1):629
pubmed: 28818039
Bioinformatics. 2011 Jun 15;27(12):1739-40
pubmed: 21546393
Nature. 2008 May 1;453(7191):51-5
pubmed: 18451854
Immunity. 2012 Mar 23;36(3):362-73
pubmed: 22406269
Arterioscler Thromb Vasc Biol. 2007 May;27(5):1004-13
pubmed: 17332491
Nucleic Acids Res. 2013 May 1;41(10):e108
pubmed: 23558742
J Immunother Cancer. 2018 Jun 18;6(1):57
pubmed: 29914571
Nat Med. 2008 May;14(5):518-27
pubmed: 18438415
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Eur J Immunol. 2011 Feb;41(2):291-8
pubmed: 21267999
J Inflamm (Lond). 2010 Feb 05;7(1):10
pubmed: 20181103
Front Immunol. 2013 Apr 08;4:85
pubmed: 23580000
Immunology. 2013 Apr;138(4):402-10
pubmed: 23278551
Eur J Immunol. 2006 Apr;36(4):864-74
pubmed: 16544275
Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2097-103
pubmed: 22772752
Genome Biol. 2010;11(3):R25
pubmed: 20196867
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Immunity. 2019 Sep 17;51(3):561-572.e5
pubmed: 31402260
Nature. 2009 Jun 4;459(7247):717-21
pubmed: 19412164
J Exp Med. 2004 Dec 6;200(11):1395-405
pubmed: 15583013
J Immunol. 2008 May 1;180(9):6288-96
pubmed: 18424752
Nucleic Acids Res. 1999 Jan 1;27(1):29-34
pubmed: 9847135
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Bioinformatics. 2017 Feb 1;33(3):414-424
pubmed: 27694195
Int J Mol Sci. 2018 Dec 02;19(12):
pubmed: 30513816
J Immunol. 2009 Aug 1;183(3):1767-79
pubmed: 19587009
J Am Soc Nephrol. 2012 Sep;23(9):1528-37
pubmed: 22835488
FEBS Open Bio. 2012 Apr 17;2:76-82
pubmed: 23650583
Trends Immunol. 2003 Jun;24(6):314-9
pubmed: 12810107
Trends Mol Med. 2013 Jun;19(6):355-67
pubmed: 23601906