CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 11 2022
07 11 2022
Historique:
received:
08
03
2022
accepted:
27
10
2022
entrez:
7
11
2022
pubmed:
8
11
2022
medline:
10
11
2022
Statut:
epublish
Résumé
Alterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses.
Identifiants
pubmed: 36344546
doi: 10.1038/s41467-022-34532-x
pii: 10.1038/s41467-022-34532-x
pmc: PMC9640663
doi:
Substances chimiques
Antigens, CD1d
0
Lipids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6723Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T013710/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S005560/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C604/A25135
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13938-43
pubmed: 10570177
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1268-73
pubmed: 12540828
Nat Commun. 2020 Sep 21;11(1):4765
pubmed: 32958780
Cell Rep. 2019 Dec 10;29(11):3405-3420.e5
pubmed: 31825825
Cell Metab. 2017 Feb 7;25(2):412-427
pubmed: 28041958
Cell Metab. 2008 Jun;7(6):485-95
pubmed: 18522830
PLoS Biol. 2011 Mar;9(3):e1000598
pubmed: 21408089
Nucleic Acids Res. 2015 May 26;43(10):5033-51
pubmed: 25934804
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4312-7
pubmed: 9113986
Nature. 2005 Mar 24;434(7032):525-9
pubmed: 15791258
Cell. 2018 Jan 25;172(3):517-533.e20
pubmed: 29249358
EMBO J. 2018 Mar 1;37(5):
pubmed: 29378774
Circ Res. 2019 Dec 6;125(12):1087-1102
pubmed: 31625810
Nature. 2014 May 22;509(7501):497-502
pubmed: 24717441
Cell Metab. 2020 Jul 7;32(1):128-143.e5
pubmed: 32516576
Metabolism. 2021 Jan;114:154338
pubmed: 32791172
Immunity. 2012 Sep 21;37(3):574-87
pubmed: 22981538
Nat Immunol. 2002 Jan;3(1):55-60
pubmed: 11731798
PLoS One. 2011;6(9):e25478
pubmed: 21980475
Immunity. 2013 Jan 24;38(1):106-18
pubmed: 23273843
Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11811-6
pubmed: 16091469
Methods Mol Biol. 2019;1960:101-112
pubmed: 30798525
Nat Metab. 2021 Sep;3(9):1150-1162
pubmed: 34531575
Cell. 2018 Jan 11;172(1-2):135-146.e9
pubmed: 29328908
Elife. 2019 Dec 16;8:
pubmed: 31841113
Cell. 2015 Jul 2;162(1):170-83
pubmed: 26095250
Nat Immunol. 2015 Jan;16(1):85-95
pubmed: 25436972
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Sci Immunol. 2021 Jun 25;6(60):
pubmed: 34172588
Blood. 2010 Sep 16;116(11):1876-84
pubmed: 20530791
Cell Rep. 2017 Jun 27;19(13):2743-2755
pubmed: 28658622
J Immunol. 2005 Mar 15;174(6):3179-86
pubmed: 15749847
Cell Res. 2019 Jan;29(1):42-53
pubmed: 30514903
Cell Res. 2017 Mar;27(3):352-372
pubmed: 28084332
Nucleic Acids Res. 2021 Jan 8;49(D1):D325-D334
pubmed: 33290552
J Lipid Res. 2007 Mar;48(3):528-42
pubmed: 17142809
EMBO Rep. 2017 Jan;18(1):39-47
pubmed: 27799287
Nat Rev Immunol. 2015 Feb;15(2):104-16
pubmed: 25614320
J Exp Med. 2022 Jun 6;219(6):
pubmed: 35438721
Biochem Biophys Res Commun. 2005 Feb 25;327(4):1143-54
pubmed: 15652515
Mol Cell Biochem. 2002 Oct;239(1-2):213-9
pubmed: 12479588
Surg Infect (Larchmt). 2014 Jun;15(3):194-9
pubmed: 24801801
Sci Adv. 2020 Oct 21;6(43):
pubmed: 33087357
Nucleic Acids Res. 2018 Jan 4;46(D1):D380-D386
pubmed: 29087512
Annu Rev Immunol. 2016 May 20;34:479-510
pubmed: 26927205
Nature. 2017 Jan 5;541(7635):41-45
pubmed: 27974793
Exp Mol Med. 2014 Jun 06;46:e99
pubmed: 24903227
Cell. 2018 Jan 11;172(1-2):147-161.e12
pubmed: 29328910
Nat Immunol. 2020 Mar;21(3):298-308
pubmed: 32066953
Cell. 2015 Dec 17;163(7):1716-29
pubmed: 26686653
Immunity. 2007 Oct;27(4):597-609
pubmed: 17950005
Trends Cell Biol. 2020 Dec;30(12):979-989
pubmed: 33036870
J Cell Biol. 2009 Mar 23;184(6):817-31
pubmed: 19307598
Front Immunol. 2017 Sep 22;8:1178
pubmed: 29018445
Cell Metab. 2008 Jun;7(6):496-507
pubmed: 18522831
Annu Rev Nutr. 2014;34:281-303
pubmed: 24850384
Immunity. 2012 Mar 23;36(3):477-90
pubmed: 22406267
Br J Nutr. 2011 Sep;106(6):878-86
pubmed: 21736821