Proteomic and lipidomic profiling of demyelinating lesions identifies fatty acids as modulators in lesion recovery.
demyelination
inflammation resolution
lipids
microglia
myelin
remyelination
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 10 2021
26 10 2021
Historique:
received:
25
03
2021
revised:
24
08
2021
accepted:
06
10
2021
entrez:
27
10
2021
pubmed:
28
10
2021
medline:
11
2
2022
Statut:
ppublish
Résumé
After demyelinating injury of the central nervous system, resolution of the mounting acute inflammation is crucial for the initiation of a regenerative response. Here, we aim to identify fatty acids and lipid mediators that govern the balance of inflammatory reactions within demyelinating lesions. Using lipidomics, we identify bioactive lipids in the resolution phase of inflammation with markedly elevated levels of n-3 polyunsaturated fatty acids. Using fat-1 transgenic mice, which convert n-6 fatty acids to n-3 fatty acids, we find that reduction of the n-6/n-3 ratio decreases the phagocytic infiltrate. In addition, we observe accelerated decline of microglia/macrophages and enhanced generation of oligodendrocytes in aged mice when n-3 fatty acids are shuttled to the brain. Thus, n-3 fatty acids enhance lesion recovery and may, therefore, provide the basis for pro-regenerative medicines of demyelinating diseases in the central nervous system.
Identifiants
pubmed: 34706241
pii: S2211-1247(21)01368-1
doi: 10.1016/j.celrep.2021.109898
pmc: PMC8567315
pii:
doi:
Substances chimiques
Fatty Acids, Omega-3
0
Fatty Acids, Omega-6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109898Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests C.K. is a shareholder of Lipotype GmbH. M.J.G. is an employee of Lipotype GmbH. The authors declare no competing interests.
Références
Brain. 2008 Jul;131(Pt 7):1749-58
pubmed: 18515322
PLoS Biol. 2017 May 26;15(5):e1002605
pubmed: 28549068
FASEB J. 2019 May;33(5):6140-6153
pubmed: 30735438
Adv Exp Med Biol. 2020;1276:223-234
pubmed: 32705603
Mol Aspects Med. 2018 Dec;64:109-134
pubmed: 29305120
Mol Cell Proteomics. 2020 Sep;19(9):1575-1585
pubmed: 32616513
Front Cell Dev Biol. 2016 May 03;4:38
pubmed: 27200350
J Biol Chem. 2002 Mar 22;277(12):10090-9
pubmed: 11790796
Nature. 2014 Jun 5;510(7503):92-101
pubmed: 24899309
Nat Methods. 2020 Sep;17(9):869-870
pubmed: 32669682
Nat Methods. 2017 May;14(5):513-520
pubmed: 28394336
Cell Death Dis. 2013 Sep 12;4:e795
pubmed: 24030147
Nat Rev Immunol. 2016 Jan;16(1):51-67
pubmed: 26688348
Cell Rep. 2020 Oct 13;33(2):108247
pubmed: 33053344
Adv Drug Deliv Rev. 2020;159:198-213
pubmed: 31987838
J Neurosci. 2006 Jan 4;26(1):328-32
pubmed: 16399703
Nat Neurosci. 2015 Dec;18(12):1819-31
pubmed: 26523646
J Exp Med. 2005 Sep 19;202(6):841-51
pubmed: 16172261
Immunity. 2014 Mar 20;40(3):315-27
pubmed: 24656045
Lipids. 2019 Jan;54(1):13-23
pubmed: 30762234
Nature. 2014 May 22;509(7501):503-6
pubmed: 24828044
Acta Neuropathol. 2015 Aug;130(2):247-61
pubmed: 25943886
Bioinformatics. 2013 Dec 15;29(24):3241-2
pubmed: 24064416
Nat Rev Immunol. 2015 Aug;15(8):511-23
pubmed: 26139350
Chem Rev. 2011 Oct 12;111(10):5922-43
pubmed: 21766791
Curr Top Microbiol Immunol. 2008;318:193-212
pubmed: 18219819
Proc Natl Acad Sci U S A. 2015 Jun 16;112(24):7587-92
pubmed: 26023184
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Nat Metab. 2021 Feb;3(2):211-227
pubmed: 33619376
Front Immunol. 2018 Jan 29;9:38
pubmed: 29434586
Eur J Lipid Sci Technol. 2015 Oct;117(10):1540-1549
pubmed: 26494980
J Exp Med. 2021 Oct 4;218(10):
pubmed: 34424266
Nat Commun. 2015 Mar 02;6:6250
pubmed: 25727495
Sci Rep. 2014 Dec 12;4:7458
pubmed: 25500548
J Proteome Res. 2020 Jun 5;19(6):2511-2515
pubmed: 32338005
Brain. 2006 Dec;129(Pt 12):3165-72
pubmed: 16921173
Prog Brain Res. 2017;231:135-163
pubmed: 28554395
Biochim Biophys Acta. 2006 Jan;1761(1):121-8
pubmed: 16458590
Nat Neurosci. 2013 Sep;16(9):1211-1218
pubmed: 23872599
Chem Rev. 2011 Oct 12;111(10):5866-98
pubmed: 21936577
Nat Rev Neurosci. 2008 Nov;9(11):839-55
pubmed: 18931697
Science. 2018 Feb 9;359(6376):684-688
pubmed: 29301957
Mol Cell Proteomics. 2018 Dec;17(12):2534-2545
pubmed: 30385480
Nat Rev Neurol. 2012 Nov 5;8(11):624-34
pubmed: 23026979
Nucleic Acids Res. 2021 Jan 8;49(D1):D545-D551
pubmed: 33125081
Nat Neurosci. 2021 Apr;24(4):489-503
pubmed: 33603230
PLoS One. 2013;8(2):e55859
pubmed: 23409068
Sci Rep. 2018 Jul 18;8(1):10872
pubmed: 30022098
BMC Neurosci. 2017 Jan 24;18(1):19
pubmed: 28114887
Lancet Neurol. 2020 Aug;19(8):678-688
pubmed: 32702337
Nat Neurosci. 2021 Jan;24(1):47-60
pubmed: 33349711
Nat Rev Neurosci. 2017 Nov 16;18(12):753-769
pubmed: 29142295
Nutr Neurosci. 2021 Jul;24(7):569-579
pubmed: 31462182
Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450
pubmed: 30395289
Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Apr;1862(4):371-381
pubmed: 27480217
Prostaglandins Leukot Essent Fatty Acids. 2011 Jul;85(1):29-35
pubmed: 21530210
J Lipid Res. 2019 Mar;60(3):566-578
pubmed: 30530735
Front Aging Neurosci. 2014 Jan 27;6:7
pubmed: 24478700
Pharmacol Rev. 2018 Jan;70(1):12-38
pubmed: 29217656
Cell Rep. 2021 Mar 9;34(10):108835
pubmed: 33691116
Nat Rev Neurol. 2019 Aug;15(8):447-458
pubmed: 31256193
J Proteome Res. 2021 Jan 1;20(1):498-505
pubmed: 33332123
Trends Neurosci. 2020 Aug;43(8):596-607
pubmed: 32620289
J Exp Med. 2020 May 4;217(5):
pubmed: 32097464
Nucleic Acids Res. 2015 Jan;43(Database issue):D1057-63
pubmed: 25378336
Neurobiol Dis. 2005 Feb;18(1):166-75
pubmed: 15649707
J Exp Med. 2015 Apr 6;212(4):481-95
pubmed: 25779633
Neurosci Lett. 2019 Nov 20;713:134532
pubmed: 31589903
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
pubmed: 11309499
Cell Rep. 2020 Sep 15;32(11):108132
pubmed: 32937123
J Exp Med. 2020 May 4;217(5):
pubmed: 32078678
Exp Neurol. 2009 Jan;215(1):160-6
pubmed: 19000674
Nat Commun. 2020 Nov 30;11(1):6133
pubmed: 33257673
Biochim Biophys Acta. 2015 Apr;1851(4):397-413
pubmed: 25139562
Nat Rev Drug Discov. 2017 Sep;16(9):617-634
pubmed: 28685761
Nat Neurosci. 2011 Jan;14(1):45-53
pubmed: 21131950
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1903-7
pubmed: 21245337
Front Cell Dev Biol. 2016 Jun 28;4:71
pubmed: 27551677
Nat Protoc. 2019 Jan;14(1):68-85
pubmed: 30464214
Nat Rev Neurol. 2017 Dec;13(12):742-754
pubmed: 29146953
Bioinformatics. 2007 May 1;23(9):1164-7
pubmed: 17344241
Sci Rep. 2017 Sep 12;7(1):11263
pubmed: 28900242
Immunity. 2015 Oct 20;43(4):817-29
pubmed: 26488817
Biochim Biophys Acta. 2015 Apr;1851(4):308-30
pubmed: 25316652
Bioinformatics. 2015 Sep 1;31(17):2860-6
pubmed: 25943471
Nature. 2004 Feb 5;427(6974):504
pubmed: 14765186
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2136-41
pubmed: 19174513
Haematologica. 2020 Aug;105(8):2056-2070
pubmed: 31780628