Altered Tregs Differentiation and Impaired Autophagy Correlate to Atherosclerotic Disease.
Aldosterone
/ pharmacology
Animals
Apolipoproteins E
/ physiology
Atherosclerosis
/ immunology
Autophagy
/ drug effects
Cell Differentiation
Cell Polarity
Disease Models, Animal
Forkhead Transcription Factors
/ metabolism
Humans
Male
Mice
Mice, Inbred C57BL
Plaque, Atherosclerotic
/ immunology
T-Lymphocytes, Regulatory
/ cytology
Transforming Growth Factor beta
/ pharmacology
ApoE-KO
atherosclerosis
autophagy
plaques
regulatory T cells
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
11
10
2019
accepted:
13
02
2020
entrez:
2
4
2020
pubmed:
2
4
2020
medline:
2
3
2021
Statut:
epublish
Résumé
Atherosclerosis is a progressive vascular disease representing the primary cause of morbidity and mortality in developed countries. Formerly, atherosclerosis was considered as a mere passive accumulation of lipids in blood vessels. However, it is now clear that atherosclerosis is a complex and multifactorial disease, in which the involvement of immune cells and inflammation play a key role. A variety of studies have shown that autophagy-a cellular catalytic mechanism able to remove injured cytoplasmic components in response to cellular stress-may be proatherogenic. So far, in this context, its role has been investigated in smooth muscle cells, macrophages, and endothelial cells, while the function of this catabolic protective process in lymphocyte functionality has been overlooked. The few studies carried out so far, however, suggested that autophagy modulation in lymphocyte subsets may be functionally related to plaque formation and development. Therefore, in this research, we aimed at better clarifying the role of lymphocyte subsets, mainly regulatory T cells (Tregs), in human atherosclerotic plaques and in animal models of atherosclerosis investigating the contribution of autophagy on immune cell homeostasis. Here, we investigate basal autophagy in a mouse model of atherosclerosis, apolipoprotein E (ApoE)-knockout (KO) mice, and we analyze the role of autophagy in driving Tregs polarization. We observed defective maturation of Tregs from ApoE-KO mice in response to tumor growth factor-β (TGFβ). TGFβ is a well-known autophagy inducer, and Tregs maturation defects in ApoE-KO mice seem to be related to autophagy impairment. In this work, we propose that autophagy underlies Tregs maturation, advocating that the study of this process in atherosclerosis may open new therapeutic strategies.
Identifiants
pubmed: 32231663
doi: 10.3389/fimmu.2020.00350
pmc: PMC7082762
doi:
Substances chimiques
Apolipoproteins E
0
FOXP3 protein, human
0
Forkhead Transcription Factors
0
Transforming Growth Factor beta
0
Aldosterone
4964P6T9RB
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
350Informations de copyright
Copyright © 2020 Mandatori, Pacella, Marzolla, Mammi, Starace, Padula, Vitiello, Armani, Savoia, Taurino, De Zio, Giampietri, Piconese, Cecconi, Caprio and Filippini.
Références
Medicine (Baltimore). 2018 Oct;97(43):e12813
pubmed: 30412071
Nature. 2012 Feb 08;482(7385):395-9
pubmed: 22318520
Stem Cell Res Ther. 2016 Nov 15;7(1):166
pubmed: 27846905
J Lipid Res. 2009 Apr;50 Suppl:S178-82
pubmed: 19060252
Nat Protoc. 2007;2(7):1789-94
pubmed: 17641646
Cancer Res. 2009 Dec 1;69(23):8844-52
pubmed: 19903843
Trends Biochem Sci. 2006 Jun;31(6):342-8
pubmed: 16679021
J Mol Biol. 2016 May 8;428(9 Pt A):1681-99
pubmed: 26908221
Front Immunol. 2018 May 09;9:1023
pubmed: 29867990
Cell Mol Life Sci. 2016 Mar;73(5):901-22
pubmed: 26518635
Annu Rev Nutr. 2007;27:19-40
pubmed: 17311494
J Transl Med. 2016 May 20;14(1):146
pubmed: 27207171
Circ Res. 2010 Feb 5;106(2):363-72
pubmed: 19926874
Front Immunol. 2013 May 10;4:106
pubmed: 23675373
J Intern Med. 2014 Dec;276(6):618-32
pubmed: 25156650
J Hypertens. 2019 Nov;37(11):2232-2239
pubmed: 31205201
Lipids Health Dis. 2017 Jan 17;16(1):12
pubmed: 28095860
Int J Cardiol. 2017 Apr 1;232:233-242
pubmed: 28089144
Biomed Res Int. 2015;2015:652738
pubmed: 26448944
J Cardiovasc Med (Hagerstown). 2015 Dec;16(12):824-30
pubmed: 25575274
Immunol Rev. 2009 May;229(1):173-91
pubmed: 19426222
J Clin Invest. 2004 Nov;114(10):1398-403
pubmed: 15545987
Trends Endocrinol Metab. 2020 Mar;31(3):205-217
pubmed: 31843490
Front Cardiovasc Med. 2019 Apr 12;6:46
pubmed: 31032262
J Clin Invest. 1995 Nov;96(5):2170-9
pubmed: 7593602
Curr Atheroscler Rep. 2013 Oct;15(10):359
pubmed: 23982263
Methods Mol Biol. 2008;445:77-88
pubmed: 18425443
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2929-37
pubmed: 21960562
Clin Rev Allergy Immunol. 2016 Jun;50(3):312-32
pubmed: 26215166
Clin Chim Acta. 2012 Oct 9;413(19-20):1562-8
pubmed: 22565046
Biomed Res Int. 2015;2015:616834
pubmed: 25722984
J Immunol. 2017 Feb 1;198(3):986-992
pubmed: 28115587
Nat Cell Biol. 2018 May;20(5):521-527
pubmed: 29686264
Ann Transl Med. 2018 Apr;6(7):116
pubmed: 29955576
Circ Res. 2015 Jan 30;116(3):456-67
pubmed: 25634969
J Exp Med. 2010 Apr 12;207(4):699-709
pubmed: 20368580
J Biol Chem. 1995 Feb 3;270(5):2320-6
pubmed: 7836465
Circ Res. 2015 Jan 30;116(3):468-79
pubmed: 25634970
Autophagy. 2016;12(1):1-222
pubmed: 26799652
Annu Rev Pathol. 2014;9:73-102
pubmed: 23937439
Anesth Essays Res. 2018 Jan-Mar;12(1):1-6
pubmed: 29628544
Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):893-900
pubmed: 17272749
J Clin Invest. 2004 Jan;113(2):310-7
pubmed: 14722622
J Cardiovasc Dev Dis. 2019 Apr 27;6(2):
pubmed: 31035613
Nat Immunol. 2013 Apr;14(4):307-8
pubmed: 23507634
Eur J Immunol. 2010 Oct;40(10):2902-13
pubmed: 20806292
J Clin Invest. 2011 Oct;121(10):4138-49
pubmed: 21968112
Front Cell Infect Microbiol. 2016 Dec 12;6:174
pubmed: 28018859
J Vis Exp. 2018 Sep 26;(139):
pubmed: 30320746
Int J Stroke. 2017 Jul;12(5):560-567
pubmed: 28697713
Nature. 2011 May 19;473(7347):317-25
pubmed: 21593864
Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):E6546-E6555
pubmed: 29941600
Nutrients. 2019 Apr 11;11(4):
pubmed: 30979078
Aging Dis. 2016 Jan 02;7(1):81-9
pubmed: 26815098
J Exp Med. 2003 Dec 15;198(12):1875-86
pubmed: 14676299
J Immunol. 1995 Aug 1;155(3):1151-64
pubmed: 7636184
Autophagy. 2015 Nov 2;11(11):2014-2032
pubmed: 26391655
Nat Immunol. 2016 Mar;17(3):277-85
pubmed: 26808230
Chin Med J (Engl). 2015 Jan 5;128(1):69-74
pubmed: 25563316
Eur J Nutr. 2015 Mar;54(2):265-72
pubmed: 24830781
J Am Heart Assoc. 2013 Feb 22;2(1):e000018
pubmed: 23525413
Cell Physiol Biochem. 2015;37(4):1369-78
pubmed: 26488467
Nature. 1993 Apr 29;362(6423):801-9
pubmed: 8479518