The axis of complement C1 and nucleolus in antinuclear autoimmunity.
ANA
GAR/RGG
SLE
alarmin
complement C1
nucleolin
nucleolus autoimmunity
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
30
03
2023
accepted:
19
05
2023
medline:
28
6
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
epublish
Résumé
Antinuclear autoantibodies (ANA) are heterogeneous self-reactive antibodies that target the chromatin network, the speckled, the nucleoli, and other nuclear regions. The immunological aberration for ANA production remains partially understood, but ANA are known to be pathogenic, especially, in systemic lupus erythematosus (SLE). Most SLE patients exhibit a highly polygenic disease involving multiple organs, but in rare complement C1q, C1r, or C1s deficiencies, the disease can become largely monogenic. Increasing evidence point to intrinsic autoimmunogenicity of the nuclei. Necrotic cells release fragmented chromatins as nucleosomes and the alarmin HMGB1 is associated with the nucleosomes to activate TLRs and confer anti-chromatin autoimmunogenecity. In speckled regions, the major ANA targets Sm/RNP and SSA/Ro contain snRNAs that confer autoimmunogenecity to Sm/RNP and SSA/Ro antigens. Recently, three GAR/RGG-containing alarmins have been identified in the nucleolus that helps explain its high autoimmunogenicity. Interestingly, C1q binds to the nucleoli exposed by necrotic cells to cause protease C1r and C1s activation. C1s cleaves HMGB1 to inactive its alarmin activity. C1 proteases also degrade many nucleolar autoantigens including nucleolin, a major GAR/RGG-containing autoantigen and alarmin. It appears that the different nuclear regions are intrinsically autoimmunogenic by containing autoantigens and alarmins. However, the extracellular complement C1 complex function to dampen nuclear autoimmunogenecity by degrading these nuclear proteins.
Identifiants
pubmed: 37359557
doi: 10.3389/fimmu.2023.1196544
pmc: PMC10288996
doi:
Substances chimiques
Complement C1
0
HMGB1 Protein
0
Alarmins
0
Nucleosomes
0
Antibodies, Antinuclear
0
Autoantigens
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1196544Informations de copyright
Copyright © 2023 Wu, Chen, Teo, Wee, Wong, Cui, Chen, Leong and Lu.
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
Chromosoma. 1997 Jun;105(7-8):470-80
pubmed: 9211975
Arthritis Rheumatol. 2014 Dec;66(12):3395-403
pubmed: 25186300
Mol Cell. 2014 Nov 6;56(3):389-399
pubmed: 25514182
Auto Immun Highlights. 2017 Dec;8(1):1
pubmed: 27896669
J Exp Med. 2008 Dec 22;205(13):3007-18
pubmed: 19064698
Mol Biol Cell. 1996 Jul;7(7):1015-24
pubmed: 8862517
Nat Commun. 2010 Oct 19;1:97
pubmed: 20981025
J Cell Sci. 1993 Feb;104 ( Pt 2):327-37
pubmed: 8505363
Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9727-32
pubmed: 18621685
J Rheumatol. 2002 Jul;29(7):1543-7
pubmed: 12136917
Cancer Res. 2011 Feb 15;71(4):1418-30
pubmed: 21159662
Nat Rev Mol Cell Biol. 2007 Mar;8(3):209-20
pubmed: 17318225
Front Immunol. 2017 May 24;8:592
pubmed: 28596769
J Neurochem. 2010 Feb;112(3):733-43
pubmed: 19919576
Front Cell Dev Biol. 2020 Sep 18;8:579137
pubmed: 33072761
Cold Spring Harb Symp Quant Biol. 2006;71:395-405
pubmed: 17381322
Mol Cell Proteomics. 2010 Jan;9(1):117-30
pubmed: 19812395
Curr Biol. 2002 Jan 8;12(1):1-11
pubmed: 11790298
Nat Rev Rheumatol. 2010 Dec;6(12):683-92
pubmed: 21060334
Autoimmun Rev. 2008 Oct;8(1):5-8
pubmed: 18790092
Front Immunol. 2018 Apr 10;9:764
pubmed: 29692784
Proc Natl Acad Sci U S A. 1981 May;78(5):2737-41
pubmed: 6789322
J Immunol. 1978 Dec;121(6):2228-34
pubmed: 102692
J Immunol. 2012 May 15;188(10):4769-75
pubmed: 22490866
Int Arch Allergy Immunol. 2000 Sep;123(1):5-9
pubmed: 11014966
J Immunol. 2017 Dec 15;199(12):3981-3990
pubmed: 29070672
J Biol Chem. 2005 Nov 25;280(47):39510-4
pubmed: 16169853
Trends Cell Biol. 2003 May;13(5):255-63
pubmed: 12742169
Science. 1969 May 23;164(3882):955-7
pubmed: 5813982
J Intern Med. 2009 Jun;265(6):680-8
pubmed: 19493061
J Exp Med. 1991 Jun 1;173(6):1407-19
pubmed: 2033369
Immunity. 2006 Sep;25(3):429-40
pubmed: 16973388
Rheumatology (Oxford). 2008 Nov;47(11):1603-11
pubmed: 18611920
Autoimmun Rev. 2013 Aug;12(10):998-1003
pubmed: 23583982
J Rheumatol. 2012 Apr;39(4):787-94
pubmed: 22467948
Mol Cancer. 2013 Aug 26;12(1):95
pubmed: 23978088
Science. 2022 Apr;376(6588):44-53
pubmed: 35357919
J Autoimmun. 2008 Feb-Mar;30(1-2):5-11
pubmed: 18194728
Br Med J. 1957 Sep 28;2(5047):732-4
pubmed: 13460368
Cold Spring Harb Symp Quant Biol. 2006;71:407-17
pubmed: 17381323
Br J Dermatol. 1997 Dec;137(6):916-20
pubmed: 9470907
Nat Commun. 2016 Jun 29;7:12090
pubmed: 27354316
J Gen Virol. 2017 Aug;98(8):2128-2142
pubmed: 28758620
Mol Cell Proteomics. 2011 Oct;10(10):M111.009241
pubmed: 21778410
Auto Immun Highlights. 2016 Dec;7(1):1
pubmed: 26831867
Cell. 2017 Aug 24;170(5):913-926.e19
pubmed: 28841417
Autoimmunity. 2007 Dec;40(8):560-6
pubmed: 18075790
Curr Opin Rheumatol. 2014 Sep;26(5):482-92
pubmed: 25010439
J Autoimmun. 2015 Nov;64:125-36
pubmed: 26324017
Arthritis Rheum. 2011 Jul;63(7):1972-8
pubmed: 21425128
Nat Rev Rheumatol. 2013 May;9(5):291-300
pubmed: 23507902
Nucleic Acids Res. 2001 Aug 1;29(15):3241-7
pubmed: 11470882
Wiley Interdiscip Rev RNA. 2010 Nov-Dec;1(3):415-31
pubmed: 21956940
J Exp Med. 2005 Mar 7;201(5):703-11
pubmed: 15738055
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D158-62
pubmed: 16381836
J Autoimmun. 2013 Mar;41:25-33
pubmed: 23395425
Ann N Y Acad Sci. 2007 Aug;1109:519-30
pubmed: 17785341
Nature. 2019 Jun;570(7761):395-399
pubmed: 31168090
Am J Pathol. 1992 Apr;140(4):859-70
pubmed: 1314027
Nucleic Acids Res. 2009 Jan;37(Database issue):D181-4
pubmed: 18984612
J Immunol. 1987 Oct 15;139(8):2579-84
pubmed: 3309055
Am J Med. 1952 Nov;13(5):591-6
pubmed: 12996537
Nat Rev Immunol. 2014 Mar;14(3):166-80
pubmed: 24481336
Front Immunol. 2019 Jun 04;10:1243
pubmed: 31231380
J Immunol. 2012 Jun 1;188(11):5682-93
pubmed: 22523386
Nat Commun. 2017 Jul 17;8:16021
pubmed: 28714469
JAMA. 1964 Jan 18;187:227-8
pubmed: 14071887
Genes Dev. 1993 Aug;7(8):1609-19
pubmed: 8339936
Genes Dev. 2016 Jul 15;30(14):1598-610
pubmed: 27474438
Clin Rev Allergy Immunol. 2022 Oct;63(2):210-239
pubmed: 35258843
J Invest Dermatol. 1990 Sep;95(3):304-8
pubmed: 2384689
Arthritis Res Ther. 2003;5(2):80-93
pubmed: 12718748
Arthritis Rheum. 1971 Jul-Aug;14(4):485-92
pubmed: 5314984
Curr Opin Rheumatol. 2017 Sep;29(5):423-433
pubmed: 28509669
Arthritis Rheum. 1972 Sep-Oct;15(5):540-3
pubmed: 4117792
Am J Gastroenterol. 2010 Jan;105(1):125-31
pubmed: 19861957
Biochem Biophys Res Commun. 1989 Sep 15;163(2):1119-27
pubmed: 2675830
RNA Biol. 2017 Jun 3;14(6):739-751
pubmed: 27661468
J Leukoc Biol. 2012 Sep;92(3):577-91
pubmed: 22753952
Front Immunol. 2016 Feb 24;7:55
pubmed: 26941740
Science. 2003 Sep 5;301(5638):1374-7
pubmed: 12920303
Expert Rev Clin Immunol. 2010 May;6(3):461-79
pubmed: 20441431
RNA Biol. 2017 Jun 3;14(6):680-692
pubmed: 27715451
Curr Opin Cell Biol. 2002 Jun;14(3):313-8
pubmed: 12067653
J Autoimmun. 2008 Dec;31(4):362-71
pubmed: 18849143
Arthritis Rheum. 2004 Mar;50(3):892-900
pubmed: 15022332
J Rheumatol. 2006 Aug;33(8):1600-5
pubmed: 16783860
Clin Immunol Immunopathol. 1995 Jan;74(1):89-99
pubmed: 7527749
Nat Struct Mol Biol. 2017 Nov;24(11):944-953
pubmed: 28945246
Arthritis Rheum. 2012 Aug;64(8):2677-86
pubmed: 22553077
Int Rev Cytol. 2002;219:199-266
pubmed: 12211630
J Cell Biol. 1995 Dec;131(6 Pt 2):1649-58
pubmed: 8557735
Autoimmune Dis. 2014;2014:203435
pubmed: 24587899
Proc Staff Meet Mayo Clin. 1949 Apr 27;24(9):234-7
pubmed: 18119558
Arthritis Rheum. 1988 Apr;31(4):525-32
pubmed: 2451921
Springer Semin Immunopathol. 2006 Oct;28(2):119-30
pubmed: 17021721
Wiley Interdiscip Rev RNA. 2012 May-Jun;3(3):397-414
pubmed: 22065625
Arthritis Rheum. 2006 May;54(5):1557-67
pubmed: 16645989
Mol Biol Cell. 2010 Nov 1;21(21):3735-48
pubmed: 20826608
Nat Commun. 2012;3:994
pubmed: 22871813
Am J Hematol. 2004 Nov;77(3):241-9
pubmed: 15495255
Nat Struct Mol Biol. 2015 Jan;22(1):11-9
pubmed: 25565028
Arthritis Rheum. 1989 Sep;32(9):1165-9
pubmed: 2789047
Cell Death Discov. 2016 Sep 12;2:16069
pubmed: 27648302
Nucleic Acids Res. 2020 Jan 8;48(D1):D220-D225
pubmed: 31598696
Cell Rep. 2016 Oct 18;17(4):1128-1140
pubmed: 27760316
Mol Cell Biol. 2002 Jan;22(2):657-68
pubmed: 11756560
J Clin Invest. 1987 Jan;79(1):65-72
pubmed: 2432091
Nat Med. 2005 Jan;11(1):85-9
pubmed: 15619631
Front Med (Lausanne). 2022 Jun 02;9:916011
pubmed: 35721085
Ann Rheum Dis. 1986 Dec;45(12):978-86
pubmed: 3545105
Arthritis Rheum. 2003 Feb 15;49(1):85-92
pubmed: 12579598
Adv Immunol. 2000;76:227-324
pubmed: 11079100
N Engl J Med. 2001 Apr 5;344(14):1058-66
pubmed: 11287977
Chromosoma. 1990 Apr;99(2):152-60
pubmed: 2192841
N Engl J Med. 1970 May 21;282(21):1174-8
pubmed: 4909324
Mol Cell Biol. 2000 Aug;20(15):5415-24
pubmed: 10891482
Mol Cell Biol. 2009 Jun;29(11):3007-17
pubmed: 19332556
Genomics. 2009 Aug;94(2):83-8
pubmed: 19446021
J Immunol. 1987 Jan 1;138(1):128-37
pubmed: 2431053
Hum Pathol. 1978 Jan;9(1):85-91
pubmed: 344192
Arthritis Rheum. 2013 Nov;65(11):2737-47
pubmed: 24122180
J Cell Sci. 1993 Dec;106 ( Pt 4):1045-56
pubmed: 7907337
Biochem Res Int. 2011;2011:195209
pubmed: 21152184
J Exp Med. 1987 Dec 1;166(6):1627-40
pubmed: 2445893
J Biol Chem. 2015 Sep 11;290(37):22570-80
pubmed: 26231209
Clin Immunol. 2000 Oct;97(1):50-8
pubmed: 10998317
Eur J Biochem. 1996 Apr 1;237(1):153-8
pubmed: 8620867
Arthritis Rheumatol. 2019 Sep;71(9):1400-1412
pubmed: 31385462
Sci Adv. 2018 Feb 28;4(2):eaao0665
pubmed: 29503865
J Clin Pathol. 2001 Mar;54(3):187-90
pubmed: 11253128
EMBO J. 1998 Jul 1;17(13):3747-57
pubmed: 9649444
Life Sci. 1979 Aug 20;25(8):701-8
pubmed: 91938
Annu Rev Immunol. 2018 Apr 26;36:489-517
pubmed: 29400998
PLoS Genet. 2010 Mar 26;6(3):e1000889
pubmed: 20361057
Essays Biochem. 1986;22:27-68
pubmed: 3549286
Nat Cell Biol. 2018 Jul;20(7):789-799
pubmed: 29941930
Autoimmunity. 2006 Aug;39(5):367-78
pubmed: 16923536
Nucleic Acids Res. 1997 Dec 1;25(23):4740-7
pubmed: 9365252
Exp Cell Res. 1988 May;176(1):117-28
pubmed: 3286276
Clin Lab. 2012;58(3-4):329-32
pubmed: 22582508
Ann Rheum Dis. 2021 May;80(5):632-640
pubmed: 33272962
Genes Immun. 2009 Jul;10(5):373-9
pubmed: 19440199
Arthritis Rheum. 1982 Nov;25(11):1271-7
pubmed: 7138600
Trends Biochem Sci. 2005 Feb;30(2):87-96
pubmed: 15691654
J Cell Biol. 2002 May 27;157(5):743-8
pubmed: 12034768
Nat Struct Mol Biol. 2015 Nov;22(11):920-3
pubmed: 26479197
J Immunol. 1997 May 15;158(10):4525-8
pubmed: 9144462
Cancer Res. 1990 Sep 15;50(18):5987-91
pubmed: 1697505
Arch Dermatol Res. 2001 Sep;293(9):455-9
pubmed: 11758788
Mol Immunol. 2021 Apr;132:41-52
pubmed: 33545624
Eur J Immunol. 2013 Sep;43(9):2441-2450
pubmed: 23749435
Nucleic Acids Res. 2016 Jun 20;44(11):5068-82
pubmed: 27174936
J Exp Med. 2001 Sep 17;194(6):781-95
pubmed: 11560994
Arthritis Rheum. 2007 Oct;56(10):3379-86
pubmed: 17907192
Proc Staff Meet Mayo Clin. 1948 Jan 21;23(2):25-8
pubmed: 18921142
Autoimmun Rev. 2007 Aug;6(7):432-7
pubmed: 17643929
J Exp Med. 1991 Nov 1;174(5):1239-44
pubmed: 1940801
Front Immunol. 2018 Oct 30;9:2496
pubmed: 30459768
Cell. 2017 May 18;169(5):780-791
pubmed: 28525751
Int Rev Cytol. 2006;251:159-208
pubmed: 16939780
Nucleic Acids Res. 2016 Sep 19;44(16):7884-95
pubmed: 27257078
Annu Rev Immunol. 2010;28:367-88
pubmed: 20192808
J Exp Med. 1998 Jul 20;188(2):387-92
pubmed: 9670050
J Rheumatol. 2000 Jan;27(1):142-8
pubmed: 10648030
Curr Rheumatol Rep. 2019 Jan 23;21(1):3
pubmed: 30673885
J Cell Sci. 1981 Dec;52:373-89
pubmed: 7334062
J Biol Chem. 2018 Feb 16;293(7):2358-2369
pubmed: 29301938
Annu Rev Biochem. 2015;84:93-129
pubmed: 25706898
Cancer Epidemiol Biomarkers Prev. 1998 Dec;7(12):1109-15
pubmed: 9865429
Proc Natl Acad Sci U S A. 1972 Nov;69(11):3394-8
pubmed: 4508329
Genomics. 1995 May 20;27(2):320-8
pubmed: 7557999
J Clin Invest. 1967 May;46(5):735-45
pubmed: 4960935
Curr Opin Immunol. 2016 Dec;43:1-7
pubmed: 27504587
J Immunol. 1966 Mar;96(3):464-71
pubmed: 5932578
J Exp Med. 1987 Mar 1;165(3):750-62
pubmed: 3546581
J Clin Invest. 1966 Nov;45(11):1732-40
pubmed: 4959277
Ann Intern Med. 1993 Nov 15;119(10):1005-13
pubmed: 8214977
Rheum Dis Clin North Am. 1988 Apr;14(1):1-14
pubmed: 3041483
Arthritis Rheum. 2003 Jan;48(1):210-7
pubmed: 12528121
Autoimmun Rev. 2012 Aug;11(10):771-5
pubmed: 22381917
Chromosome Res. 2019 Mar;27(1-2):109-127
pubmed: 30656516
J Clin Immunol. 2002 Mar;22(2):98-105
pubmed: 11998899
Arthritis Res. 2001;3(2):102-6
pubmed: 11178117
Biol Cell. 1985;54(2):123-33
pubmed: 2933102
J Rheumatol. 2012 Nov;39(11):2104-10
pubmed: 22942262
Arthritis Rheumatol. 2017 Jan;69(1):35-45
pubmed: 27785888
Mol Biol Rep. 1996;23(3-4):227-34
pubmed: 9112233
J Cell Biol. 2002 Oct 14;159(1):17-21
pubmed: 12379800
J Cell Sci. 1992 Aug;102 ( Pt 4):729-37
pubmed: 1429888
J Cell Sci. 2002 Aug 15;115(Pt 16):3297-307
pubmed: 12140261
Cell Death Dis. 2021 May 12;12(5):477
pubmed: 33980825
Clin Exp Immunol. 1994 Oct;98(1):35-9
pubmed: 7923881
J Cell Biol. 1999 Aug 9;146(3):559-72
pubmed: 10444065
Cold Spring Harb Perspect Biol. 2022 Feb 1;14(2):
pubmed: 34400553
Int J Rheum Dis. 2015 Feb;18(2):192-9
pubmed: 25522798
Clin Exp Immunol. 2002 Dec;130(3):532-40
pubmed: 12452846
Ann Rheum Dis. 2002 Sep;61(9):842-6
pubmed: 12176814
Proc Natl Acad Sci U S A. 1986 Nov;83(22):8689-93
pubmed: 2430297
Immunol Med. 2019 Mar;42(1):1-9
pubmed: 31204893
J Transl Autoimmun. 2022 Jan 19;5:100145
pubmed: 35128372
Autoimmun Rev. 2003 Oct;2(6):313-21
pubmed: 14550872