TLR9 ligand sequestration by chemokine CXCL4 negatively affects central B cell tolerance.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 12 2023
04 12 2023
Historique:
received:
31
05
2023
revised:
07
08
2023
accepted:
09
08
2023
pmc-release:
29
03
2024
medline:
2
10
2023
pubmed:
29
9
2023
entrez:
29
9
2023
Statut:
ppublish
Résumé
Central B cell tolerance is believed to be regulated by B cell receptor signaling induced by the recognition of self-antigens in immature B cells. Using humanized mice with defective MyD88, TLR7, or TLR9 expression, we demonstrate that TLR9/MYD88 are required for central B cell tolerance and the removal of developing autoreactive clones. We also show that CXCL4, a chemokine involved in systemic sclerosis (SSc), abrogates TLR9 function in B cells by sequestering TLR9 ligands away from the endosomal compartments where this receptor resides. The in vivo production of CXCL4 thereby impedes both TLR9 responses in B cells and the establishment of central B cell tolerance. We conclude that TLR9 plays an essential early tolerogenic function required for the establishment of central B cell tolerance and that correcting defective TLR9 function in B cells from SSc patients may represent a novel therapeutic strategy to restore B cell tolerance.
Identifiants
pubmed: 37773045
pii: 276305
doi: 10.1084/jem.20230944
pmc: PMC10541333
pii:
doi:
Substances chimiques
Ligands
0
Myeloid Differentiation Factor 88
0
Platelet Factor 4
37270-94-3
Toll-Like Receptor 7
0
Toll-Like Receptor 9
0
Tlr9 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI132447
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI071087
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI061093
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL151970
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR050401
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2023 Çakan et al.
Références
Immunol Rev. 2019 Nov;292(1):90-101
pubmed: 31721234
Nature. 2018 Aug;560(7718):387-391
pubmed: 29925955
Cytokine Growth Factor Rev. 2011 Feb;22(1):1-18
pubmed: 21111666
J Exp Med. 2005 Mar 7;201(5):703-11
pubmed: 15738055
Nat Commun. 2017 Oct 13;8(1):913
pubmed: 29030552
Nat Rev Immunol. 2006 Nov;6(11):823-35
pubmed: 17063184
Bioinformatics. 2018 Sep 1;34(17):i884-i890
pubmed: 30423086
J Clin Invest. 2017 May 1;127(5):1651-1663
pubmed: 28346226
J Immunol. 2013 Feb 15;190(4):1447-56
pubmed: 23296704
Ann Intern Med. 1982 May;96(5):610-3
pubmed: 6176160
J Clin Invest. 2020 Jun 1;130(6):3172-3187
pubmed: 32191633
J Exp Med. 2005 May 16;201(10):1659-67
pubmed: 15897279
J Exp Med. 2000 Jun 5;191(11):1813-7
pubmed: 10839798
Arthritis Res Ther. 2016 Dec 30;18(1):305
pubmed: 28038680
Nature. 2007 Oct 4;449(7162):564-9
pubmed: 17873860
Arthritis Rheumatol. 2018 Mar;70(3):450-461
pubmed: 29193892
Cell Rep. 2017 Feb 14;18(7):1627-1635
pubmed: 28199836
Blood. 2015 Mar 12;125(11):1749-58
pubmed: 25631768
J Rheumatol. 1988 Feb;15(2):202-5
pubmed: 3361530
Arthritis Rheumatol. 2022 Feb;74(2):307-317
pubmed: 34279059
Sci Immunol. 2016;1(1):
pubmed: 27917411
Sci Rep. 2018 Jun 21;8(1):9466
pubmed: 29930254
J Exp Med. 2006 Aug 7;203(8):1999-2008
pubmed: 16864658
Nat Immunol. 2010 May;11(5):373-84
pubmed: 20404851
Science. 2003 Sep 5;301(5638):1374-7
pubmed: 12920303
Sci Immunol. 2021 Aug 19;6(62):
pubmed: 34413140
Nat Commun. 2019 May 1;10(1):1731
pubmed: 31043596
J Exp Med. 2022 Jul 4;219(7):
pubmed: 35640018
J Biol Chem. 2013 May 10;288(19):13522-33
pubmed: 23536183
Drug Metab Dispos. 2012 Jul;40(7):1429-40
pubmed: 22517972
J Clin Invest. 2013 Oct;123(10):4283-93
pubmed: 24051380
Nature. 2005 Apr 21;434(7036):1035-40
pubmed: 15815647
J Immunol. 2015 Feb 15;194(4):1403-7
pubmed: 25601924
Bioinformatics. 2016 Sep 15;32(18):2847-9
pubmed: 27207943
Immunity. 2006 Sep;25(3):417-28
pubmed: 16973389
JAMA. 2020 Aug 18;324(7):663-673
pubmed: 32706371
J Immunol. 2003 May 1;170(9):4465-74
pubmed: 12707322
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Sci Transl Med. 2018 Jan 10;10(423):
pubmed: 29321259
Front Immunol. 2013 Sep 06;4:266
pubmed: 24046769
Arthritis Rheum. 2008 Jul;58(7):2163-73
pubmed: 18576347
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2264-71
pubmed: 8637861
J Immunol. 2002 Jul 1;169(1):159-66
pubmed: 12077241
Immunity. 2008 Nov 14;29(5):746-57
pubmed: 19006693
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Proc Natl Acad Sci U S A. 2021 Jul 6;118(27):
pubmed: 34215697
Nat Commun. 2017 Nov 13;8(1):1462
pubmed: 29133782
Immunity. 2015 Nov 17;43(5):884-95
pubmed: 26546282
Cell Rep. 2023 Jan 31;42(1):111930
pubmed: 36640356
Nat Immunol. 2022 Oct;23(10):1457-1469
pubmed: 36151396
N Engl J Med. 2014 Jan 30;370(5):433-43
pubmed: 24350901
Blood. 2016 Jul 21;128(3):371-83
pubmed: 27222476
JCI Insight. 2018 Mar 8;3(5):
pubmed: 29515028
J Clin Invest. 2011 Sep;121(9):3635-44
pubmed: 21804190