Dietary Supplementation With Eicosapentaenoic Acid Inhibits Plasma Cell Differentiation and Attenuates Lupus Autoimmunity.
Animals
Autoantibodies
/ immunology
Autoimmunity
/ drug effects
B-Lymphocytes
/ drug effects
Cell Differentiation
/ drug effects
Cells, Cultured
Dietary Supplements
Disease Models, Animal
Eicosapentaenoic Acid
/ administration & dosage
Female
Kidney
/ drug effects
Lupus Erythematosus, Systemic
/ immunology
Mice, Inbred C57BL
Mice, Knockout
Plasma Cells
/ drug effects
autoantibody
autoimmunity
fatty acid
immunometabolism
membrane dynamics
plasma cells
systemic lupus erythematosus
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
08
01
2021
accepted:
26
05
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
28
9
2021
Statut:
epublish
Résumé
Accumulating evidence suggests that cholesterol accumulation in leukocytes is causally associated with the development of autoimmune diseases. However, the mechanism by which fatty acid composition influences autoimmune responses remains unclear. To determine whether the fatty acid composition of diet modulates leukocyte function and the development of systemic lupus erythematosus, we examined the effect of eicosapentaenoic acid (EPA) on the pathology of lupus in drug-induced and spontaneous mouse models. We found that dietary EPA supplementation ameliorated representative lupus manifestations, including autoantibody production and immunocomplex deposition in the kidneys. A combination of lipidomic and membrane dynamics analyses revealed that EPA remodels the lipid composition and fluidity of B cell membranes, thereby preventing B cell differentiation into autoantibody-producing plasma cells. These results highlight a previously unrecognized mechanism by which fatty acid composition affects B cell differentiation into autoantibody-producing plasma cells during autoimmunity, and imply that EPA supplementation may be beneficial for therapy of lupus.
Identifiants
pubmed: 34211460
doi: 10.3389/fimmu.2021.650856
pmc: PMC8240640
doi:
Substances chimiques
Autoantibodies
0
Eicosapentaenoic Acid
AAN7QOV9EA
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
650856Informations de copyright
Copyright © 2021 Kobayashi, Ito, Shirakawa, Tamura, Tomono, Shindou, Hedde, Tanaka, Tsuboi, Ishimoto, Akashi-Takamura, Maruyama and Suganami.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Cell. 2008 Jul 11;134(1):97-111
pubmed: 18614014
Clin Med Insights Arthritis Musculoskelet Disord. 2016 May 22;9:81-7
pubmed: 27257397
Immunity. 2009 Aug 21;31(2):245-58
pubmed: 19646905
Exp Biol Med (Maywood). 2013 Jun;238(6):610-22
pubmed: 23918873
Ann Rheum Dis. 2013 Dec;72(12):2011-7
pubmed: 24114925
J Clin Invest. 2017 Oct 2;127(10):3640-3651
pubmed: 28846071
J Immunol. 2014 Dec 15;193(12):6031-40
pubmed: 25392529
Br J Clin Pharmacol. 2013 Mar;75(3):645-62
pubmed: 22765297
Cell Metab. 2017 Jun 6;25(6):1294-1304.e6
pubmed: 28479366
Immunity. 2016 Dec 20;45(6):1311-1326
pubmed: 28002731
Nat Rev Immunol. 2005 Mar;5(3):230-42
pubmed: 15738953
Cell Metab. 2013 Nov 5;18(5):685-97
pubmed: 24206663
Microb Pathog. 2020 Apr;141:103979
pubmed: 31954822
Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2561-5
pubmed: 23077142
Nature. 2014 Jun 5;510(7503):92-101
pubmed: 24899309
Elife. 2015 Jul 14;4:e08009
pubmed: 26173179
Science. 2014 May 2;344(6183):519-23
pubmed: 24786080
Precis Clin Med. 2020 Mar;3(1):34-43
pubmed: 32257532
Sci Rep. 2014 Sep 18;4:6406
pubmed: 25230773
Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov;79(3-5):101-8
pubmed: 18951005
Biophys J. 2013 Mar 19;104(6):1238-47
pubmed: 23528083
Nat Commun. 2020 Mar 12;11(1):1339
pubmed: 32165635
J Biol Chem. 1957 May;226(1):497-509
pubmed: 13428781
Nat Rev Endocrinol. 2018 Aug;14(8):452-463
pubmed: 29904174
Arthritis Rheum. 2012 Feb;64(2):493-503
pubmed: 21905015
Nat Immunol. 2020 Jun;21(6):605-614
pubmed: 32367037
Front Immunol. 2018 Mar 05;9:427
pubmed: 29556239
Nat Med. 2008 Jul;14(7):748-55
pubmed: 18542049
Front Immunol. 2019 Sep 27;10:2241
pubmed: 31611873
J Biomed Biotechnol. 2011;2011:271694
pubmed: 21403825
Metabolites. 2019 Oct 21;9(10):
pubmed: 31640217
Lupus. 2016 Jun;25(7):727-34
pubmed: 26811368
J Nutr. 1999 Feb;129(2):328-35
pubmed: 10024609
J Nutr Biochem. 2011 Aug;22(8):784-90
pubmed: 21111596
Mol Immunol. 2013 Dec;56(4):574-82
pubmed: 23911415
Arthritis Rheumatol. 2014 Mar;66(3):694-706
pubmed: 24574230
J Lipid Res. 2010 Jun;51(6):1284-97
pubmed: 20071694
Lupus. 2007;16(9):731-5
pubmed: 17728367
PLoS One. 2015 Aug 07;10(8):e0135081
pubmed: 26252021
J Lipid Res. 2013 Nov;54(11):3130-8
pubmed: 23986558
Br J Nutr. 1992 Jan;67(1):17-26
pubmed: 1547199
Life Sci. 2018 Jun 15;203:255-267
pubmed: 29715470
PLoS One. 2013 Nov 07;8(11):e78874
pubmed: 24244380
J Nutr. 2011 Jun;141(6):1041-8
pubmed: 21525263
Arthritis Rheum. 2006 Jan;54(1):115-26
pubmed: 16385503
Cell. 2016 Apr 21;165(3):551-65
pubmed: 27040498
Arthritis Rheumatol. 2018 Dec;70(12):2025-2035
pubmed: 29938934
Cell. 2010 Sep 3;142(5):687-98
pubmed: 20813258
Int J Mol Sci. 2019 Oct 11;20(20):
pubmed: 31614433
Arthritis Res Ther. 2014 May 14;16(3):R112
pubmed: 24886807