Microbial metabolite butyrate promotes induction of IL-10+IgM+ plasma cells.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
05
11
2021
accepted:
11
03
2022
entrez:
25
3
2022
pubmed:
26
3
2022
medline:
6
5
2022
Statut:
epublish
Résumé
The microbially-derived short-chain fatty acid butyrate is a central inhibitor of inflammatory innate and adaptive immune responses. Emerging evidence suggests that butyrate induces differentiation of IL-10-producing (IL-10+) regulatory B cells. However, the underlying mechanisms of butyrate-driven modulation of B cell differentiation are not fully defined. Given the dominant role of regulatory plasma cells (PCs) as the main source of anti-inflammatory cytokines including IL-10 and the observation that butyrate also induces the differentiation of PCs, we here investigated the effect of the microbial metabolite butyrate on the induction of regulatory IL-10+ PCs and underlying mechanisms. Here we show that butyrate induces the differentiation of IL-10+IgM+ PCs. Ex vivo, butyrate, but hardly propionate, another microbially-derived short-chain fatty acid, induced the differentiation of IL-10+IgM+ CD138high PCs from isolated splenic murine B cells. In vivo, administration of butyrate via drinking water or by daily intraperitoneal injection increased the number of IL-10+IgM+ CD138high PCs in the spleens of Ovalbumin (Ova)/complete Freund's adjuvant-immunized mice. The induction of these regulatory PCs was associated with an increase of anti-Ova IgM, but a reduction of anti-Ova class-switched pathogenic IgG2b serum antibodies. Based on the knowledge that butyrate inhibits histone deacetylases (HDACs) thereby increasing histone acetylation, we identified here that HDAC3 inhibition was sufficient to induce PC differentiation and IL-10+ expression. Furthermore, reduced mitochondrial superoxide levels following butyrate treatment and HDAC3 inhibition were necessary for PC differentiation, but not IL-10 expression. In summary, the microbial metabolite butyrate promotes the differentiation of IgM+ PCs and their expression of IL-10. HDAC3 inhibition may be involved as an underlying pathway for both PC differentiation and IL-10 expression, while reduced mitochondrial superoxide levels are crucial only for PC differentiation. The induction of regulatory IL-10+IgM+ PCs and the inhibition of class switching to antigen-specific pathogenic IgG subclasses might represent important pathways of butyrate to limit inflammation.
Identifiants
pubmed: 35333906
doi: 10.1371/journal.pone.0266071
pii: PONE-D-21-35353
pmc: PMC8956175
doi:
Substances chimiques
Butyrates
0
Fatty Acids, Volatile
0
Immunoglobulin M
0
Superoxides
11062-77-4
Interleukin-10
130068-27-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0266071Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Front Immunol. 2018 Jun 06;9:1183
pubmed: 29928274
Cell Metab. 2020 Apr 7;31(4):837-851.e10
pubmed: 32213346
Front Biosci. 2007 Jan 01;12:1722-36
pubmed: 17127417
EMBO Rep. 2012 May 01;13(5):440-7
pubmed: 22422004
Mucosal Immunol. 2018 May;11(3):785-795
pubmed: 29067994
Nature. 2014 Mar 20;507(7492):366-370
pubmed: 24572363
Immunity. 2005 Jul;23(1):41-51
pubmed: 16039578
J Anim Sci. 2018 Dec 3;96(12):5244-5252
pubmed: 30252114
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2247-52
pubmed: 24390544
Biochem Pharmacol. 2006 Sep 28;72(7):881-92
pubmed: 16899228
Diabetes. 2017 May;66(5):1405-1418
pubmed: 28223285
Nat Rev Immunol. 2016 May 27;16(6):341-52
pubmed: 27231050
Cell Res. 2020 Jun;30(6):492-506
pubmed: 32433595
Nat Immunol. 2003 Apr;4(4):321-9
pubmed: 12612580
Int Immunol. 2015 Oct;27(10):479-86
pubmed: 26071023
J Nutr Biochem. 2011 Sep;22(9):849-55
pubmed: 21167700
Mucosal Immunol. 2021 Jan;14(1):4-13
pubmed: 33106585
Front Immunol. 2018 Jul 17;9:1584
pubmed: 30065721
Curr Allergy Asthma Rep. 2016 Nov;16(11):79
pubmed: 27796794
Nat Med. 2014 Feb;20(2):159-66
pubmed: 24390308
Immunity. 2010 Nov 24;33(5):777-90
pubmed: 21093317
Science. 2013 Aug 2;341(6145):569-73
pubmed: 23828891
Cancer Biol Ther. 2010 Jun 1;9(11):853-61
pubmed: 20364116
Trends Mol Med. 2020 Sep;26(9):862-873
pubmed: 32402849
Development. 2014 Nov;141(22):4206-18
pubmed: 25371358
Immunity. 2004 May;20(5):517-27
pubmed: 15142521
J Immunol. 2009 Dec 1;183(11):7514-22
pubmed: 19917676
Front Immunol. 2021 Feb 15;12:628453
pubmed: 33659009
Nature. 2013 Dec 19;504(7480):451-5
pubmed: 24226773
J Immunol. 2002 Nov 15;169(10):5866-73
pubmed: 12421969
Allergy. 2014 Nov;69(11):1454-63
pubmed: 25060230
Mol Cell. 2016 Dec 1;64(5):982-992
pubmed: 27889451
Pediatr Res. 2020 Jan;87(2):378-384
pubmed: 31731288
Immunity. 2015 Apr 21;42(4):607-12
pubmed: 25902480
Gut Microbes. 2012 Jan-Feb;3(1):4-14
pubmed: 22356853
Diabetes. 2009 Jul;58(7):1509-17
pubmed: 19366864
J Vis Exp. 2016 Nov 21;(117):
pubmed: 27911401
Cell. 2000 Sep 1;102(5):553-63
pubmed: 11007474
Immunity. 2014 Dec 18;41(6):1040-51
pubmed: 25484301
J Nutr. 2003 Jul;133(7 Suppl):2485S-2493S
pubmed: 12840228
Trends Immunol. 2017 May;38(5):358-372
pubmed: 28385520
J Exp Med. 2020 Jul 6;217(7):
pubmed: 32374402
Nutr Res. 2008 May;28(5):321-8
pubmed: 19083427
Nat Commun. 2018 Apr 27;9(1):1698
pubmed: 29703886
Clin Exp Immunol. 2016 Jan;183(1):65-75
pubmed: 26352785
Cell Host Microbe. 2016 Aug 10;20(2):202-14
pubmed: 27476413
J Allergy Clin Immunol. 2018 Jan;141(1):399-402.e8
pubmed: 28728998
Cell Rep. 2016 Jun 21;15(12):2809-24
pubmed: 27332875
Nature. 2009 Oct 29;461(7268):1282-6
pubmed: 19865172
Mol Cell. 2020 Oct 1;80(1):43-58.e7
pubmed: 32937100
Gut. 1987 Oct;28(10):1221-7
pubmed: 3678950
J Biol Chem. 2010 Sep 3;285(36):27601-8
pubmed: 20601425
Front Immunol. 2018 May 09;9:958
pubmed: 29867943
Immunity. 2002 Jul;17(1):51-62
pubmed: 12150891
J Lipid Res. 2013 Sep;54(9):2325-40
pubmed: 23821742
Front Biol (Beijing). 2014 Aug;9(4):269-282
pubmed: 25506356
Br J Pharmacol. 2011 Oct;164(4):1079-106
pubmed: 21371012
Immunity. 2006 Jan;24(1):19-28
pubmed: 16413920
J Exp Med. 2014 Oct 20;211(11):2169-81
pubmed: 25288399
J Immunol Res. 2019 Oct 27;2019:7546047
pubmed: 31772949
Immunity. 2019 Feb 19;50(2):432-445.e7
pubmed: 30683619
Front Immunol. 2019 Mar 11;10:277
pubmed: 30915065
Curr Opin Pharmacol. 2015 Aug;23:1-5
pubmed: 25978519
Cell. 2016 Jun 2;165(6):1332-1345
pubmed: 27259147
Immunology. 2018 Jun;154(2):220-229
pubmed: 29569377
Nat Immunol. 2002 Oct;3(10):944-50
pubmed: 12244307
Bioorg Med Chem Lett. 2010 Jan 15;20(2):493-8
pubmed: 20005104
Nat Commun. 2020 Jan 2;11(1):60
pubmed: 31896754
Front Immunol. 2018 Jul 06;9:1525
pubmed: 30034392
Clin Sci (Lond). 2009 Sep 01;117(9):331-8
pubmed: 19335337
Nat Commun. 2016 Nov 23;7:13419
pubmed: 27876802
PLoS One. 2014 May 09;9(5):e96246
pubmed: 24817082
J Allergy Clin Immunol. 2020 Sep;146(3):652-666.e11
pubmed: 32445838
J Immunol. 2009 Aug 15;183(4):2312-20
pubmed: 19620304
Glycobiology. 2020 Mar 20;30(4):241-253
pubmed: 32103252
Biomed J. 2019 Aug;42(4):233-242
pubmed: 31627865
PLoS One. 2011 Feb 28;6(2):e17234
pubmed: 21386904
Nat Commun. 2019 Feb 15;10(1):760
pubmed: 30770822
J Autoimmun. 2021 May;119:102611
pubmed: 33631650
Nat Commun. 2015 Apr 10;6:6750
pubmed: 25857523
EBioMedicine. 2020 Aug;58:102913
pubmed: 32711255