title: Requirements for innate immune pathways in environmentally induced autoimmunity.
abstract: There is substantial evidence that environmental triggers in combination with genetic and stochastic factors play an important role in spontaneous autoimmune disease. Although the specific environmental agents and how they promote autoimmunity remain largely unknown, in part because of diverse etiologies, environmentally induced autoimmune models can provide insights into potential mechanisms. Studies of idiopathic and environmentally induced systemic autoimmunity show that they are mediated by common adaptive immune response genes. By contrast, although the innate immune system is indispensable for autoimmunity, there are clear differences in the molecular and cellular innate components that mediate specific systemic autoimmune diseases, suggesting distinct autoimmune-promoting pathways. Some of these differences may be related to the bifurcation of toll-like receptor signaling that distinguishes interferon regulatory factor 7-mediated type I interferon production from nuclear factor-κB-driven proinflammatory cytokine expression. Accordingly, idiopathic and pristane-induced systemic autoimmunity require both type I interferon and proinflammatory cytokines whereas the less aggressive mercury-induced autoimmunity, although dependent on nucleic acid-binding toll-like receptors, does not require type I interferon but needs proinflammatory cytokines. Scavenger receptors and the inflammasome may contribute to silica-induced autoimmunity. Greater understanding of the innate mechanisms responsible for idiopathic and environmentally induced autoimmunity should yield new information into the processes that instigate and drive systemic autoimmunity.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. mpollard@scripps.edu
authors.forename: Kenneth Michael
authors.initials: KM
authors.lastname: Pollard
authors.forename: Dwight H
authors.initials: DH
authors.lastname: Kono
mesh_terms: D056704:Adaptive Immunity; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004785:Environmental Pollutants / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants
references.citation: Eur J Immunol. 2008 Jul;38(7):1948-60
references.pmid: 18506882
references.citation: Histochem J. 1996 Mar;28(3):217-25
references.pmid: 8735289
references.citation: Toxicol Sci. 2009 Apr;108(2):462-71
references.pmid: 19151164
references.citation: J Autoimmun. 2010 Jun;34(4):339-48
references.pmid: 19944565
references.citation: Cell Mol Immunol. 2007 Aug;4(4):261-8
references.pmid: 17764616
references.citation: Am J Pathol. 2006 Apr;168(4):1227-40
references.pmid: 16565497
references.citation: Nat Rev Rheumatol. 2009 Aug;5(8):448-56
references.pmid: 19597511
references.citation: J Immunol. 1998 Jul 1;161(1):234-40
references.pmid: 9647229
references.citation: J Autoimmun. 2012 Dec;39(4):323-31
references.pmid: 22578563
references.citation: J Immunol. 2000 Aug 15;165(4):2263-70
references.pmid: 10925315
references.citation: Trends Mol Med. 2007 Nov;13(11):460-9
references.pmid: 18029230
references.citation: J Autoimmun. 2007 Mar-May;28(2-3):114-21
references.pmid: 17368845
references.citation: Nature. 1988 Jan 28;331(6154):356-8
references.pmid: 2893286
references.citation: J Autoimmun. 2003 Feb;20(1):15-25
references.pmid: 12604309
references.citation: Clin Exp Immunol. 2009 Mar;155(3):567-76
references.pmid: 19077085
references.citation: J Immunol. 1999 Sep 15;163(6):3153-9
references.pmid: 10477582
references.citation: Sci Signal. 2010 Jan 19;3(105):cm1
references.pmid: 20086235
references.citation: J Immunol. 2010 Oct 15;185(8):4738-49
references.pmid: 20844193
references.citation: Toxicol Sci. 2010 Aug;116(2):682-92
references.pmid: 20513754
references.citation: Int Arch Allergy Immunol. 2000 Sep;123(1):77-91
references.pmid: 11014974
references.citation: Free Radic Biol Med. 2008 Apr 1;44(7):1246-58
references.pmid: 18226603
references.citation: Chem Res Toxicol. 2010 Mar 15;23(3):455-66
references.pmid: 20078109
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L107-13
references.pmid: 16997884
references.citation: Ann Rheum Dis. 2011 Mar;70 Suppl 1:i64-i66
references.pmid: 21339222
references.citation: Toxicology. 2008 Apr 18;246(2-3):172-9
references.pmid: 18295955
references.citation: Kidney Int. 2001 Dec;60(6):2173-80
references.pmid: 11737591
references.citation: Autoimmunity. 2005 Nov;38(7):497-506
references.pmid: 16373255
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9035-40
references.pmid: 18577586
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2610-5
references.pmid: 12604793
references.citation: J Leukoc Biol. 2010 Sep;88(3):547-57
references.pmid: 20576854
references.citation: Am J Ind Med. 2011 Apr;54(4):255-62
references.pmid: 20957678
references.citation: PLoS One. 2011 Feb 02;6(2):e14647
references.pmid: 21311600
references.citation: J Exp Med. 2003 Mar 17;197(6):777-88
references.pmid: 12642605
references.citation: J Exp Med. 2006 Aug 7;203(8):1999-2008
references.pmid: 16864658
references.citation: Lupus. 1996 Feb;5(1):62-9
references.pmid: 8646229
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Aug;289(2):L186-95
references.pmid: 15849212
references.citation: Science. 2010 Jan 15;327(5963):291-5
references.pmid: 20075244
references.citation: J Exp Med. 1998 Sep 7;188(5):985-90
references.pmid: 9730900
references.citation: Nat Rev Immunol. 2008 Aug;8(8):594-606
references.pmid: 18641647
references.citation: J Clin Invest. 2007 Aug;117(8):2186-96
references.pmid: 17641780
references.citation: Int Immunopharmacol. 2001 Mar;1(3):581-93
references.pmid: 11367541
references.citation: Immunity. 2011 Mar 25;34(3):352-63
references.pmid: 21435586
references.citation: Autoimmunity. 2012 Dec;45(8):602-11
references.pmid: 22917079
references.citation: Arthritis Rheum. 2002 Jul;46(7):1840-50
references.pmid: 12124868
references.citation: Trends Immunol. 2009 Sep;30(9):455-64
references.pmid: 19699150
references.citation: Nat Rev Rheumatol. 2010 Mar;6(3):146-56
references.pmid: 20142813
references.citation: Arthritis Rheum. 2007 Nov;56(11):3770-83
references.pmid: 17968932
references.citation: Am J Pathol. 1994 May;144(5):927-37
references.pmid: 8178944
references.citation: J Immunol. 2005 Mar 1;174(5):2499-506
references.pmid: 15728455
references.citation: Environ Health Insights. 2010 May 18;4:21-6
references.pmid: 20523881
references.citation: Arthritis Res Ther. 2010;12 Suppl 1:S5
references.pmid: 21303493
references.citation: Lancet. 2012 May 26;379(9830):2008-18
references.pmid: 22534002
references.citation: Arthritis Rheum. 2007 May;56(5):1721; author reply 1721-2
references.pmid: 17469167
references.citation: J Biol Chem. 2006 Nov 10;281(45):34218-26
references.pmid: 16984918
references.citation: J Immunol. 2011 Feb 1;186(3):1747-54
references.pmid: 21191074
references.citation: J Immunol. 2004 Nov 1;173(9):5880-7
references.pmid: 15494542
references.citation: Nat Rev Immunol. 2006 Nov;6(11):823-35
references.pmid: 17063184
references.citation: J Rheumatol. 2010 Jan;37(1):60-70
references.pmid: 19955044
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7119-24
references.pmid: 19359475
references.citation: Part Fibre Toxicol. 2006 Jan 05;3:2
references.pmid: 16396683
references.citation: J Autoimmun. 2009 Nov-Dec;33(3-4):231-8
references.pmid: 19846276
references.citation: Autoimmun Rev. 2005 Jun;4(5):282-8
references.pmid: 15990075
references.citation: Science. 2010 Feb 5;327(5966):656-61
references.pmid: 20133564
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3402-7
references.pmid: 17360658
references.citation: Nature. 2005 Mar 10;434(7030):243-9
references.pmid: 15665823
references.citation: Eur J Immunol. 2012 Jun;42(6):1477-87
references.pmid: 22678902
references.citation: Immunol Rev. 2010 Mar;234(1):76-89
references.pmid: 20193013
references.citation: Arthritis Rheum. 2009 Apr;60(4):1096-101
references.pmid: 19333924
references.citation: Nat Immunol. 2010 May;11(5):373-84
references.pmid: 20404851
references.citation: Blood. 2007 Jan 15;109(2):703-10
references.pmid: 16973958
references.citation: J Clin Invest. 1998 Jan 15;101(2):364-71
references.pmid: 9435308
references.citation: Rheumatology (Oxford). 2010 Nov;49(11):2172-80
references.pmid: 20675707
references.citation: Immunology. 2006 Nov;119(3):296-305
references.pmid: 17067309
references.citation: Nature. 2008 Mar 13;452(7184):234-8
references.pmid: 18305481
references.citation: Inhal Toxicol. 2004 Mar;16(3):133-9
references.pmid: 15204774
references.citation: J Immunol. 2010 Feb 15;184(4):1840-8
references.pmid: 20089701
references.citation: Annu Rev Immunol. 2005;23:307-36
references.pmid: 15771573
references.citation: Arthritis Rheum. 2007 May;56(5):1618-28
references.pmid: 17469144
references.citation: J Immunol. 2012 Dec 15;189(12):5976-84
references.pmid: 23175700
references.citation: Nature. 2005 Jun 2;435(7042):590-7
references.pmid: 15931211
references.citation: Pulm Med. 2011;2011:105707
references.pmid: 21660282
references.citation: J Immunol. 2009 Feb 15;182(4):1982-90
references.pmid: 19201851
references.citation: Clin J Am Soc Nephrol. 2010 Mar;5(3):439-44
references.pmid: 20089494
references.citation: J Immunol. 2004 Aug 1;173(3):2134-42
references.pmid: 15265950
references.citation: J Exp Med. 2008 Dec 22;205(13):2995-3006
references.pmid: 19047436
references.citation: J Immunol. 2010 Jun 1;184(11):6367-77
references.pmid: 20421647
references.citation: Nature. 2005 Apr 21;434(7036):1035-40
references.pmid: 15815647
references.citation: Arthritis Rheum. 2012 Oct;64(10):3399-408
references.pmid: 22674120
references.citation: J Exp Med. 2005 Jul 18;202(2):321-31
references.pmid: 16027240
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12061-6
references.pmid: 19574451
references.citation: Curr Opin Immunol. 2012 Dec;24(6):665-70
references.pmid: 22999705
references.citation: Lupus. 1997;6(1):1-3
references.pmid: 9116713
references.citation: Neurosci Lett. 1999 Aug 20;271(2):93-6
references.pmid: 10477110
references.citation: Nat Rev Immunol. 2001 Nov;1(2):147-53
references.pmid: 11905822
references.citation: Nat Immunol. 2006 Feb;7(2):156-64
references.pmid: 16415873
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3012-7
references.pmid: 20133703
references.citation: Ann Rheum Dis. 2011 Nov;70(11):2029-36
references.pmid: 21803750
references.citation: Immunity. 2006 Sep;25(3):417-28
references.pmid: 16973389
references.citation: J Immunol. 2010 Nov 15;185(10):6003-12
references.pmid: 20935208
references.citation: J Immunotoxicol. 2008 Apr;5(2):129-37
references.pmid: 18569382
references.citation: J Autoimmun. 2010 Dec;35(4):291-8
references.pmid: 20810248
references.citation: Nature. 1969 Jun 7;222(5197):994-5
references.pmid: 5789334
references.citation: J Immunol. 1988 Jul 1;141(1):118-24
references.pmid: 3259964
references.citation: J Immunol. 2006 Oct 15;177(8):5687-96
references.pmid: 17015758
references.citation: J Autoimmun. 2012 May;38(2-3):J177-86
references.pmid: 22137891
references.citation: J Immunol. 2003 May 1;170(9):4465-74
references.pmid: 12707322
references.citation: Agents Actions. 1993;39 Spec No:C117-20
references.pmid: 8273548
references.citation: Kidney Int. 2003 Sep;64(3):897-905
references.pmid: 12911539
references.citation: Clin Exp Immunol. 2005 Aug;141(2):238-47
references.pmid: 15996188
references.citation: Eur J Immunol. 2000 Jul;30(7):2038-47
references.pmid: 10940893
references.citation: Am J Pathol. 2009 Nov;175(5):2023-33
references.pmid: 19808647
references.citation: Arch Immunol Ther Exp (Warsz). 2010 Oct;58(5):355-64
references.pmid: 20676786
references.citation: J Immunol. 2004 Oct 1;173(7):4744-54
references.pmid: 15383612
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19973-8
references.pmid: 21045126
references.citation: Immunopharmacology. 1995 Aug;30(2):131-7
references.pmid: 8530254
references.citation: Arthritis Rheum. 2006 Nov;54(11):3648-54
references.pmid: 17075811
references.citation: Cold Spring Harb Perspect Biol. 2012 Mar 01;4(3):
references.pmid: 22296764
references.citation: Arthritis Res Ther. 2009;11(4):R112
references.pmid: 19624844
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):E898-904
references.pmid: 22431588
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5044-9
references.pmid: 17360358
references.citation: Arthritis Rheum. 2011 Jan;63(1):219-29
references.pmid: 20954185
references.citation: Immunogenetics. 2011 May;63(5):291-308
references.pmid: 21229240
references.citation: J Exp Med. 2001 Dec 17;194(12):F59-63
references.pmid: 11748288
references.citation: J Autoimmun. 2012 Dec;39(4):253-8
references.pmid: 22771005
references.citation: J Immunol. 2009 Nov 1;183(9):6021-9
references.pmid: 19812195
references.citation: Mol Immunol. 1995 May;32(7):495-503
references.pmid: 7783752
references.citation: J Exp Med. 2007 Oct 1;204(10):2259-65
references.pmid: 17893199
references.citation: Arthritis Rheum. 2008 Apr;58(4):1107-15
references.pmid: 18383384
references.citation: Environ Res. 2010 May;110(4):345-54
references.pmid: 20176347
references.citation: Science. 2010 Nov 19;330(6007):1061-4
references.pmid: 21097929
references.citation: J Autoimmun. 2012 Dec;39(4):285-93
references.pmid: 22748431
references.citation: Discov Med. 2011 Jun;11(61):513-20
references.pmid: 21712017
references.citation: Eur J Immunol. 2006 May;36(5):1296-308
references.pmid: 16541466
references.citation: Science. 2010 Sep 17;329(5998):1530-4
references.pmid: 20847273
references.citation: J Autoimmun. 2011 Feb;36(1):4-8
references.pmid: 20708902
references.citation: Clin Immunol Immunopathol. 1989 Sep;52(3):421-34
references.pmid: 2758698
references.citation: Arthritis Rheum. 2006 Jan;54(1):336-42
references.pmid: 16385525
references.citation: J Immunol. 2008 Apr 1;180(7):5101-8
references.pmid: 18354236
references.citation: Autoimmun Rev. 2010 Nov;10(1):3-7
references.pmid: 20863908
references.citation: J Immunol. 2011 Nov 1;187(9):4835-43
references.pmid: 21930960
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10154-9
references.pmid: 20479222
references.citation: J Autoimmun. 2012 Dec;39(4):259-71
references.pmid: 22739348
references.citation: Nature. 2005 Apr 7;434(7034):772-7
references.pmid: 15800576
references.citation: Nat Rev Immunol. 2011 Nov 18;11(12):807-22
references.pmid: 22094985
references.citation: FASEB J. 2008 Jun;22(6):2053-63
references.pmid: 18180331
references.citation: J Immunol. 2012 Apr 15;188(8):4113-21
references.pmid: 22422888
references.citation: Trends Cell Biol. 2009 Sep;19(9):455-64
references.pmid: 19716304
references.citation: Int J Immunogenet. 2011 Oct;38(5):411-7
references.pmid: 21834935
references.citation: Am J Respir Crit Care Med. 2002 Feb 15;165(4):527-33
references.pmid: 11850347
references.citation: J Environ Pathol Toxicol Oncol. 2001;20 Suppl 1:53-65
references.pmid: 11570674
references.citation: J Immunol. 2009 Feb 15;182(4):2532-41
references.pmid: 19201910
references.citation: Lupus. 2010 Aug;19(9):1012-9
references.pmid: 20693194
references.citation: Hong Kong Med J. 2006 Aug;12(4):316-8
references.pmid: 16912361
references.citation: J Immunol. 2012 Oct 1;189(7):3741-50
references.pmid: 22933628
references.citation: J Immunotoxicol. 2010 Oct-Dec;7(4):268-78
references.pmid: 20849352
references.citation: Nat Commun. 2012 Apr 03;3:767
references.pmid: 22473011
references.citation: Inhal Toxicol. 2010 Jan;22(1):77-83
references.pmid: 20017595
references.citation: Rheumatology (Oxford). 2005 Sep;44(9):1101-7
references.pmid: 15928001
references.citation: Science. 2008 May 2;320(5876):674-7
references.pmid: 18403674
references.citation: Immunity. 2010 Dec 14;33(6):967-78
references.pmid: 21167752
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2940-5
references.pmid: 23382217
references.citation: Nat Med. 2007 May;13(5):543-51
references.pmid: 17479100
references.citation: J Immunol. 2012 Jan 15;188(2):902-15
references.pmid: 22147767
references.citation: Clin Exp Immunol. 2003 Mar;131(3):415-21
references.pmid: 12605693
references.citation: Genes Immun. 2006 Oct;7(7):555-67
references.pmid: 16900204
references.citation: Lupus. 2009 Apr;18(5):413-7
references.pmid: 19318393
references.citation: J Tongji Med Univ. 1997;17(1):18-20, 24
references.pmid: 9639778
references.citation: J Interferon Cytokine Res. 2011 Dec;31(12):867-86
references.pmid: 22029446
references.citation: Springer Semin Immunopathol. 2006 Oct;28(2):83-96
references.pmid: 16972052
references.citation: J Am Soc Nephrol. 1993 Jul;4(1):58-61
references.pmid: 8400070
references.citation: Environ Health. 2004 Nov 02;3(1):11
references.pmid: 15522122
references.citation: Annu Rev Immunol. 2009;27:519-50
references.pmid: 19302047
references.citation: Toxicology. 2005 Apr 15;209(2):135-47
references.pmid: 15767026