title: Toll-like receptors in systemic lupus erythematosus: potential targets for therapeutic intervention.
abstract: Toll-like receptors (TLRs) have attracted increased attention in recent years, not only for their role in sensing conserved microbial components, but also in the realm of autoimmunity. Although TLRs are most widely known for their capacity to detect conserved motifs of infectious agents, mounting evidence indicates that these innate receptors also promote autoimmune conditions by causing uncontrolled autoinflammation as a result of chronic recognition of self. In response to the need for modern approaches to treatment of autoimmune diseases, several groups have begun investigating ways to target TLRs as new therapeutic options for autoimmune conditions. Here we discuss recent data describing advances in TLRs as therapeutic targets for treatment of autoimmune diseases, with a focus on systemic lupus erythematosus.
authors.affiliation: Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. christopher-horton@ouhsc.edu
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Horton
authors.forename: A Darise
authors.initials: AD
authors.lastname: Farris
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D004247:DNA / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D051193:Toll-Like Receptors / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D009696:Nucleic Acids; D051193:Toll-Like Receptors; D004247:DNA
references.citation: J Clin Endocrinol Metab. 2008 Feb;93(2):578-83
references.pmid: 18029454
references.citation: Nat Genet. 2008 Sep;40(9):1062-4
references.pmid: 19165919
references.citation: Rheumatology (Oxford). 2008 Feb;47(2):145-9
references.pmid: 18160420
references.citation: Ann Rheum Dis. 2010 Jun;69(6):1195-9
references.pmid: 19674980
references.citation: Annu Rev Immunol. 2001;19:623-55
references.pmid: 11244049
references.citation: J Immunol. 2009 Nov 15;183(10):6207-16
references.pmid: 19841185
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7971-6
references.pmid: 12799462
references.citation: J Clin Invest. 2010 Oct;120(10):3651-62
references.pmid: 20811154
references.citation: Immunity. 2007 Aug;27(2):321-33
references.pmid: 17707128
references.citation: Science. 2003 Aug 1;301(5633):640-3
references.pmid: 12855817
references.citation: Mol Immunol. 2007 Jul;44(14):3453-61
references.pmid: 17477969
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9970-5
references.pmid: 16777955
references.citation: Mol Immunol. 2009 Nov;47(1):12-8
references.pmid: 19232437
references.citation: Nat Immunol. 2004 Oct;5(10):971-4
references.pmid: 15454919
references.citation: Arthritis Res Ther. 2007;9(6):222
references.pmid: 18086320
references.citation: Science. 2003 Jun 6;300(5625):1524-5
references.pmid: 12791976
references.citation: Lupus. 2005;14(6):417-22
references.pmid: 16038103
references.citation: Arthritis Rheum. 1998 Jul;41(7):1241-50
references.pmid: 9663482
references.citation: Ann N Y Acad Sci. 2008 Nov;1143:1-20
references.pmid: 19076341
references.citation: J Rheumatol. 2007 Mar;34(3):493-500
references.pmid: 17295441
references.citation: Eur J Immunol. 2001 Nov;31(11):3388-93
references.pmid: 11745357
references.citation: Eur J Immunol. 2007 Feb;37(2):306-9
references.pmid: 17273997
references.citation: Nat Immunol. 2001 Aug;2(8):675-80
references.pmid: 11477402
references.citation: Nat Rev Immunol. 2007 May;7(5):353-64
references.pmid: 17457343
references.citation: Science. 2006 Jun 16;312(5780):1669-72
references.pmid: 16709748
references.citation: Biochemistry. 2008 Sep 23;47(38):10010-7
references.pmid: 18759459
references.citation: Genes Dev. 2001 Sep 15;15(18):2321-42
references.pmid: 11562344
references.citation: Ann Rheum Dis. 2011 Nov;70(11):1905-13
references.pmid: 21798883
references.citation: Genes Immun. 2009 Jul;10(5):470-7
references.pmid: 19387456
references.citation: Curr Top Microbiol Immunol. 2007;316:359-86
references.pmid: 17969456
references.citation: J Immunol. 2005 May 1;174(9):5193-200
references.pmid: 15843514
references.citation: Arthritis Rheum. 2005 Feb;52(2):651-8
references.pmid: 15692999
references.citation: Ann N Y Acad Sci. 2004 Dec;1037:170-4
references.pmid: 15699513
references.citation: Arthritis Rheum. 2006 Nov;54(11):3601-11
references.pmid: 17075805
references.citation: J Exp Med. 2011 Jun 6;208(6):1215-28
references.pmid: 21606507
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15838-43
references.pmid: 20733074
references.citation: J Exp Med. 2005 Oct 17;202(8):1131-9
references.pmid: 16230478
references.citation: FEBS Lett. 2003 Jul 31;548(1-3):103-7
references.pmid: 12885415
references.citation: Arthritis Rheum. 2000 Jul;43(7):1431-42
references.pmid: 10902743
references.citation: J Am Soc Nephrol. 2007 Jun;18(6):1721-31
references.pmid: 17460144
references.citation: Cell. 2002 Jul 26;110(2):191-202
references.pmid: 12150927
references.citation: J Biol Chem. 2005 Apr 22;280(16):15809-14
references.pmid: 15755740
references.citation: Clin Exp Immunol. 2009 May;156(2):285-93
references.pmid: 19292767
references.citation: Eur J Immunol. 2011 Aug;41(8):2176-84
references.pmid: 21604257
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):233-8
references.pmid: 14679297
references.citation: Int Immunol. 2006 Jul;18(7):1101-13
references.pmid: 16728431
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: J Exp Med. 2007 May 14;204(5):1025-36
references.pmid: 17470642
references.citation: J Exp Med. 2001 Sep 17;194(6):863-9
references.pmid: 11561001
references.citation: Immunity. 2006 Sep;25(3):417-28
references.pmid: 16973389
references.citation: Rheumatology (Oxford). 2005 Nov;44(11):1456-7
references.pmid: 16188944
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: Arthritis Rheum. 2009 Sep;60(9):2767-71
references.pmid: 19714644
references.citation: Tissue Antigens. 2005 Mar;65(3):266-70
references.pmid: 15730519
references.citation: Nat Genet. 2011 Mar;43(3):253-8
references.pmid: 21336280
references.citation: Arthritis Rheum. 2005 Aug;52(8):2313-22
references.pmid: 16052591
references.citation: Nat Immunol. 2004 Oct;5(10):1061-8
references.pmid: 15361868
references.citation: J Rheumatol. 2007 Aug;34(8):1708-11
references.pmid: 17516623
references.citation: Rheumatology (Oxford). 2010 Dec;49(12):2281-9
references.pmid: 20739362
references.citation: Arthritis Rheum. 2006 Apr;54(4):1279-82
references.pmid: 16575840
references.citation: Genes Immun. 2009 Jul;10(5):373-9
references.pmid: 19440199
references.citation: Arthritis Rheum. 1982 Apr;25(4):401-6
references.pmid: 6176248
references.citation: Eur J Immunol. 2007 Dec;37(12):3582-6
references.pmid: 18034431
references.citation: Ann Rheum Dis. 2010 Oct;69(10):1861-5
references.pmid: 20525845
references.citation: Nature. 2010 Jun 17;465(7300):937-41
references.pmid: 20559388
references.citation: Nature. 2002 Apr 18;416(6882):750-6
references.pmid: 11923871
references.citation: Lupus. 2008 May;17(5):394-9
references.pmid: 18490415
references.citation: Trends Immunol. 2009 Aug;30(8):383-91
references.pmid: 19643665
references.citation: Nat Rev Drug Discov. 2010 Apr;9(4):293-307
references.pmid: 20380038
references.citation: Nat Genet. 2008 Sep;40(9):1059-61
references.pmid: 19165918
references.citation: Mol Syst Biol. 2006;2:2006.0015
references.pmid: 16738560
references.citation: Arthritis Res Ther. 2011 Mar 11;13(2):R41
references.pmid: 21396113
references.citation: Nat Immunol. 2004 May;5(5):495-502
references.pmid: 15107846
references.citation: Springer Semin Immunopathol. 1992;14(2):141-57
references.pmid: 1475741
references.citation: Mol Cell. 1998 Aug;2(2):253-8
references.pmid: 9734363
references.citation: Curr Top Med Chem. 2009;9(8):724-37
references.pmid: 19689377
references.citation: J Immunol. 2009 Jun 1;182(11):7244-53
references.pmid: 19454721
references.citation: Semin Immunol. 2007 Feb;19(1):24-32
references.pmid: 17275323
references.citation: J Exp Med. 2003 Mar 17;197(6):711-23
references.pmid: 12642603