Expression of H
Hv1 channel
NOX2 complex
ROS
immunosuppression
myeloid cells
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
12 04 2022
12 04 2022
Historique:
entrez:
4
4
2022
pubmed:
5
4
2022
medline:
16
4
2022
Statut:
ppublish
Résumé
Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population with high immunosuppressive activity that proliferates in infections, inflammation, and tumor microenvironments. In tumors, MDSC exert immunosuppression mainly by producing reactive oxygen species (ROS), a process triggered by the NADPH oxidase 2 (NOX2) activity. NOX2 is functionally coupled with the Hv1 proton channel in certain immune cells to support sustained free-radical production. However, a functional expression of the Hv1 channel in MDSC has not yet been reported. Here, we demonstrate that mouse MDSC express functional Hv1 proton channel by immunofluorescence microscopy, flow cytometry, and Western blot, besides performing a biophysical characterization of its macroscopic currents via patch-clamp technique. Our results show that the immunosuppression by MDSC is conditional to their ability to decrease the proton concentration elevated by the NOX2 activity, rendering Hv1 a potential drug target for cancer treatment.
Identifiants
pubmed: 35377790
doi: 10.1073/pnas.2104453119
pmc: PMC9169626
doi:
Substances chimiques
Hv1 proton channel, mouse
0
Ion Channels
0
Protons
0
Reactive Oxygen Species
0
Cybb protein, mouse
EC 1.6.3.-
NADPH Oxidase 2
EC 1.6.3.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2104453119Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL047678
Pays : United States
Organisme : HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL152201
Organisme : NHLBI NIH HHS
ID : R56 HL138103
Pays : United States
Organisme : HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL138103
Organisme : HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL47678
Organisme : NHLBI NIH HHS
ID : R01 HL152201
Pays : United States
Références
Nature. 2006 Apr 27;440(7088):1213-6
pubmed: 16554753
Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9971-6
pubmed: 24912149
Cancer Res. 2001 Jun 15;61(12):4756-60
pubmed: 11406548
J Physiol. 2005 Dec 1;569(Pt 2):419-31
pubmed: 16195320
Biochem Biophys Res Commun. 2013 Aug 23;438(2):312-7
pubmed: 23891691
PLoS One. 2020 May 6;15(5):e0227522
pubmed: 32374759
Cancer Immunol Res. 2017 Jan;5(1):3-8
pubmed: 28052991
Cancer Res. 2006 Apr 1;66(7):3629-38
pubmed: 16585188
Cell. 2006 Jul 14;126(1):205-18
pubmed: 16839887
Sci Immunol. 2016 Aug;1(2):
pubmed: 28417112
Cancer Res. 2004 Aug 15;64(16):5839-49
pubmed: 15313928
Cancer Immunol Immunother. 2015 Dec;64(12):1587-99
pubmed: 26497849
Nat Rev Immunol. 2012 Jul 13;12(8):557-69
pubmed: 22790179
Int Immunopharmacol. 2011 Jul;11(7):802-7
pubmed: 21237299
Am J Physiol Cell Physiol. 2012 Jul 15;303(2):C204-12
pubmed: 22572846
Mol Pharmacol. 2016 Sep;90(3):385-402
pubmed: 27260771
Nat Med. 2007 Jul;13(7):828-35
pubmed: 17603493
Biochem Biophys Res Commun. 2009 May 1;382(2):274-9
pubmed: 19285483
Oxid Med Cell Longev. 2016;2016:1580967
pubmed: 27547291
Blood. 2008 Apr 15;111(8):4233-44
pubmed: 18272812
Immunol Res. 2013 Dec;57(1-3):172-84
pubmed: 24203443
Proteomics. 2016 Jan;16(2):367-78
pubmed: 26403437
J Immunol Methods. 2012 Jul 31;381(1-2):14-22
pubmed: 22522114
J Gen Physiol. 2016 Feb;147(2):127-36
pubmed: 26809792
Cell. 2018 Feb 8;172(4):825-840.e18
pubmed: 29336888
Biophys J. 1996 Jul;71(1):182-93
pubmed: 8804602
Nat Struct Mol Biol. 2010 Jan;17(1):51-6
pubmed: 20023639
Pflugers Arch. 2017 Feb;469(2):251-261
pubmed: 28013412
J Gen Physiol. 1995 Jun;105(6):861-96
pubmed: 7561747
Proc Natl Acad Sci U S A. 2018 Sep 11;115(37):9240-9245
pubmed: 30127012
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7642-7
pubmed: 19372380
Physiology (Bethesda). 2010 Feb;25(1):27-40
pubmed: 20134026
J Immunol. 1991 Nov 15;147(10):3638-45
pubmed: 1940362
J Exp Med. 2010 Oct 25;207(11):2439-53
pubmed: 20876310
Cancer Immunol Immunother. 2019 Apr;68(4):631-644
pubmed: 29785656
Biochem Biophys Res Commun. 2011 Aug 26;412(2):353-9
pubmed: 21821008
Cancer Res. 2010 Jan 1;70(1):68-77
pubmed: 20028852
J Leukoc Biol. 2003 Aug;74(2):186-96
pubmed: 12885935
J Immunol. 2009 May 1;182(9):5693-701
pubmed: 19380816
J Leukoc Biol. 2012 Jan;91(1):167-81
pubmed: 21954284
Cancer Res. 2012 Jun 1;72(11):2746-56
pubmed: 22593198
Curr Opin Immunol. 2010 Apr;22(2):238-44
pubmed: 20171075
Ann Oncol. 2019 Jan 1;30(1):44-56
pubmed: 30395155
J Physiol. 2001 Sep 15;535(Pt 3):767-81
pubmed: 11559774
Proc Natl Acad Sci U S A. 2021 May 11;118(19):
pubmed: 33941706
Biomed Pharmacother. 2021 Jan;133:110978
pubmed: 33176269
J R Soc Interface. 2018 Apr;15(141):
pubmed: 29643227
J Biol Chem. 2012 Apr 20;287(17):13877-88
pubmed: 22367212
Trends Immunol. 2016 Mar;37(3):208-220
pubmed: 26858199
Nat Commun. 2016 Jul 06;7:12150
pubmed: 27381735
PLoS One. 2013 Aug 05;8(8):e70550
pubmed: 23940591
Nature. 2003 Apr 3;422(6931):531-4
pubmed: 12673252
J Gen Physiol. 2003 Jun;121(6):615-28
pubmed: 12771195
Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):E5962-E5971
pubmed: 27647906
J Immunol. 1999 May 15;162(10):5728-37
pubmed: 10229805
J Immunol. 2016 Apr 15;196(8):3470-8
pubmed: 26936880
J Immunol Methods. 1994 May 2;171(1):131-7
pubmed: 8176234
Immunol Rev. 2008 Apr;222:162-79
pubmed: 18364001
Immunol Rev. 2013 Sep;255(1):210-21
pubmed: 23947357
Int J Cancer. 2014 Jun 15;134(12):2853-64
pubmed: 24259296
Microbiol Spectr. 2016 Jun;4(3):
pubmed: 27337449
Science. 2006 Apr 28;312(5773):589-92
pubmed: 16556803