title: Small RNA regulators of T cell-mediated autoimmunity.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are short singlestranded RNA molecules that regulate gene expression post-transcriptionally. Several hundred miRNAs exist in the mammalian genome and regulate developmental processes, cell cycle, and survival.
  
  
  METHODS
  In this review,we highlight generalmodes of miRNA function and relate them to how such regulation can be beneficial for immune homeostasis and the prevention of autoimmune diseases.We highlight examples of experimentally verified miRNA function and their target genes in the immune system and place them in context of concepts relevant to an understanding of autoimmune pathogenesis. Where available, we refer to clinical correlations. Finally, we speculate how emerging knowledge about miRNA function in the immune system might be used diagnostically and therapeutically.
authors.affiliation: Diabetes Center and the Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Lukas T
authors.initials: LT
authors.lastname: Jeker
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D015551:Autoimmunity / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D012333:RNA, Messenger / Q000276:immunology*; D034741:RNA, Small Interfering / Q000276:immunology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering
references.citation: Nature. 2007 Feb 15;445(7129):766-70
references.pmid: 17220876
references.citation: Immunity. 2009 May;30(5):646-55
references.pmid: 19464987
references.citation: J Autoimmun. 2009 May-Jun;32(3-4):189-94
references.pmid: 19303254
references.citation: Mol Cell. 2008 May 23;30(4):460-71
references.pmid: 18498749
references.citation: Nat Immunol. 2009 Jul;10(7):689-95
references.pmid: 19536194
references.citation: Science. 2001 Jul 13;293(5528):240-5
references.pmid: 11452112
references.citation: Immunity. 2007 Dec;27(6):847-59
references.pmid: 18055230
references.citation: Nat Rev Immunol. 2009 Mar;9(3):207-13
references.pmid: 19151748
references.citation: Cell. 2008 Mar 7;132(5):860-74
references.pmid: 18329371
references.citation: Immunity. 2009 Nov 20;31(5):772-86
references.pmid: 19896394
references.citation: J Autoimmun. 2007 Dec;29(4):206-12
references.pmid: 17904335
references.citation: J Immunol. 2009 Aug 15;183(4):2506-12
references.pmid: 19625646
references.citation: Nature. 2005 Feb 17;433(7027):769-73
references.pmid: 15685193
references.citation: Nat Immunol. 2009 Nov;10(11):1162-9
references.pmid: 19801983
references.citation: Cell. 2007 Oct 5;131(1):146-59
references.pmid: 17923094
references.citation: Int Rev Immunol. 2009;28(3-4):112-38
references.pmid: 19811318
references.citation: Nat Genet. 2007 Mar;39(3):380-5
references.pmid: 17259983
references.citation: Cell. 2009 Jan 9;136(1):26-36
references.pmid: 19135886
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7797-802
references.pmid: 18509048
references.citation: J Exp Med. 2008 Sep 1;205(9):1993-2004
references.pmid: 18725526
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7080-5
references.pmid: 17438277
references.citation: J Exp Med. 2008 Sep 1;205(9):2005-17
references.pmid: 18725527
references.citation: Nat Immunol. 2009 Sep;10(9):1000-7
references.pmid: 19633673
references.citation: Nat Rev Genet. 2004 May;5(5):396-400
references.pmid: 15143321
references.citation: Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39
references.pmid: 19165215
references.citation: Nature. 2009 Jan 22;457(7228):426-33
references.pmid: 19158789
references.citation: Nat Genet. 2009 Jun;41(6):703-7
references.pmid: 19430480
references.citation: Science. 2008 Sep 12;321(5895):1490-2
references.pmid: 18787168
references.citation: Genome Res. 2009 Jan;19(1):92-105
references.pmid: 18955434
references.citation: Science. 2001 Oct 26;294(5543):862-4
references.pmid: 11679672
references.citation: J Exp Med. 2009 Aug 3;206(8):1643-6
references.pmid: 19635860
references.citation: J Exp Med. 2007 Oct 29;204(11):2553-9
references.pmid: 17938233
references.citation: Nature. 2009 Mar 19;458(7236):351-6
references.pmid: 19182775
references.citation: Science. 2009 Mar 13;323(5920):1488-92
references.pmid: 19286559
references.citation: Nat Rev Immunol. 2009 Nov;9(11):811-6
references.pmid: 19809471
references.citation: Immunity. 1995 Nov;3(5):541-7
references.pmid: 7584144
references.citation: Nature. 2006 Dec 7;444(7120):724-9
references.pmid: 17086201
references.citation: Cell. 2009 Feb 20;136(4):577-80
references.pmid: 19239877
references.citation: Cell. 2007 Apr 20;129(2):303-17
references.pmid: 17397913
references.citation: Mol Cell. 2007 Jul 6;27(1):91-105
references.pmid: 17612493
references.citation: Proc Natl Acad Sci U S A. 1986 Aug;83(15):5372-6
references.pmid: 16593734
references.citation: J Exp Med. 2006 Oct 30;203(11):2519-27
references.pmid: 17060477
references.citation: Cell Cycle. 2009 Mar 15;8(6):853-9
references.pmid: 19221492
references.citation: Science. 2010 Jan 15;327(5963):291-5
references.pmid: 20075244
references.citation: Eur J Immunol. 2010 Mar;40(3):888-98
references.pmid: 20148420
references.citation: Immunity. 2008 Jul 18;29(1):44-56
references.pmid: 18585065
references.citation: Science. 2007 Apr 27;316(5824):604-8
references.pmid: 17463289
references.citation: Science. 2009 Jan 23;323(5913):502-5
references.pmid: 19164748
references.citation: Nat Immunol. 2008 Apr;9(4):405-14
references.pmid: 18327259
references.citation: Nat Genet. 2008 Dec;40(12):1478-83
references.pmid: 18978791
references.citation: Nature. 2007 Jul 5;448(7149):83-6
references.pmid: 17589500
references.citation: Diabetes. 2010 Feb;59(2):407-15
references.pmid: 19875613
references.citation: Science. 1999 Nov 26;286(5445):1735-8
references.pmid: 10576740
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10266-71
references.pmid: 19509335
references.citation: Nature. 2010 Jan 14;463(7278):191-6
references.pmid: 20016485
references.citation: Science. 2009 Nov 13;326(5955):986-91
references.pmid: 19797626
references.citation: Nat Rev Immunol. 2008 Jan;8(1):9-21
references.pmid: 18097446
references.citation: J Immunol. 2009 Jan 1;182(1):259-73
references.pmid: 19109157
references.citation: Nat Genet. 2007 Sep;39(9):1074-82
references.pmid: 17676041
references.citation: Science. 2007 Apr 27;316(5824):608-11
references.pmid: 17463290
references.citation: Nature. 2005 Dec 1;438(7068):685-9
references.pmid: 16258535
references.citation: Nature. 2005 Jun 2;435(7042):584-9
references.pmid: 15931210
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1608-13
references.pmid: 18227514
references.citation: Science. 2010 Feb 26;327(5969):1098-102
references.pmid: 20185720
references.citation: Mol Cell. 2009 Sep 11;35(5):610-25
references.pmid: 19748357
references.citation: Genes Dev. 2007 Aug 15;21(16):1983-8
references.pmid: 17699747
references.citation: Cell. 1984 Apr;36(4):1007-15
references.pmid: 6323013
references.citation: Annu Rev Immunol. 2005;23:601-49
references.pmid: 15771582
references.citation: Nat Immunol. 2009 Dec;10(12):1252-9
references.pmid: 19838199
references.citation: Cell. 2008 Mar 7;132(5):875-86
references.pmid: 18329372
references.citation: PLoS Genet. 2007 Dec;3(12):e215
references.pmid: 18085825
references.citation: Immunity. 2009 Jan 16;30(1):80-91
references.pmid: 19144316
references.citation: Science. 2001 Oct 26;294(5543):853-8
references.pmid: 11679670
references.citation: J Exp Med. 2005 Jul 18;202(2):261-9
references.pmid: 16009718
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: Immunity. 1995 Oct;3(4):521-30
references.pmid: 7584142
references.citation: J Exp Med. 2005 Mar 7;201(5):723-35
references.pmid: 15753206
references.citation: Nat Genet. 2001 Jan;27(1):68-73
references.pmid: 11138001
references.citation: Nature. 2009 Jun 18;459(7249):1010-4
references.pmid: 19458619
references.citation: Nat Med. 2005 Feb;11(2):138-45
references.pmid: 15654326
references.citation: Arthritis Res Ther. 2008;10(4):R101
references.pmid: 18759964
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10898-903
references.pmid: 16040801
references.citation: J Exp Med. 2005 May 2;201(9):1367-73
references.pmid: 15867090
references.citation: Immunity. 2009 Jan 16;30(1):155-67
references.pmid: 19144320
references.citation: Nature. 2005 Jun 2;435(7042):590-7
references.pmid: 15931211
references.citation: Curr Opin Immunol. 2009 Jun;21(3):281-5
references.pmid: 19500966
references.citation: Nature. 1985 Feb 21-27;313(6004):703-6
references.pmid: 2579337
references.citation: Nature. 2008 May 22;453(7194):544-7
references.pmid: 18497826
references.citation: Cell. 2008 Aug 22;134(4):577-86
references.pmid: 18691745
references.citation: Science. 2004 Jan 2;303(5654):83-6
references.pmid: 14657504
references.citation: Nat Rev Immunol. 2004 Sep;4(9):665-74
references.pmid: 15343366
references.citation: Nat Rev Immunol. 2010 Feb;10(2):111-22
references.pmid: 20098459
references.citation: Science. 2001 Oct 26;294(5543):858-62
references.pmid: 11679671
references.citation: Nat Immunol. 2009 Jun;10(6):595-602
references.pmid: 19412181
references.citation: Blood. 2009 Dec 10;114(25):5152-61
references.pmid: 19794140
references.citation: Nature. 2010 Jan 14;463(7278):184-90
references.pmid: 20016488
references.citation: Cell. 2007 Jul 13;130(1):89-100
references.pmid: 17599402
references.citation: J Exp Med. 2008 Sep 1;205(9):1983-91
references.pmid: 18725525
references.citation: Nature. 2008 Sep 4;455(7209):58-63
references.pmid: 18668040
references.citation: Immunity. 2008 May;28(5):621-9
references.pmid: 18450484
references.citation: Nature. 1998 Feb 19;391(6669):806-11
references.pmid: 9486653
references.citation: Nat Biotechnol. 2007 Dec;25(12):1457-67
references.pmid: 18026085
references.citation: Cell. 2007 Jun 29;129(7):1401-14
references.pmid: 17604727
references.citation: Nature. 2009 May 21;459(7245):428-32
references.pmid: 19363473
references.citation: N Engl J Med. 2009 Apr 16;360(16):1646-54
references.pmid: 19369670
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Mol Cell. 2007 Oct 26;28(2):328-36
references.pmid: 17964270
references.citation: Nat Rev Genet. 2008 Feb;9(2):102-14
references.pmid: 18197166
references.citation: Immunity. 2008 May;28(5):687-97
references.pmid: 18468463
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Science. 1999 Sep 24;285(5436):2122-5
references.pmid: 10497129
references.citation: Cell. 2007 Apr 6;129(1):147-61
references.pmid: 17382377
references.citation: Immunity. 2008 May;28(5):630-8
references.pmid: 18455451
references.citation: Cell. 2009 Jun 12;137(6):1005-17
references.pmid: 19524505
references.citation: N Engl J Med. 2007 Aug 30;357(9):851-62
references.pmid: 17660530
references.citation: Cell. 2009 Apr 17;137(2):273-82
references.pmid: 19379693
references.citation: Science. 2007 Dec 21;318(5858):1931-4
references.pmid: 18048652
references.citation: PLoS Biol. 2009 Nov;7(11):e1000238
references.pmid: 19901979
references.citation: Nat Immunol. 2008 Aug;9(8):839-45
references.pmid: 18645592
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):498-502
references.pmid: 19114655
references.citation: Nature. 2008 Jul 3;454(7200):56-61
references.pmid: 18548003
references.citation: J Immunol. 2009 Mar 1;182(5):2578-82
references.pmid: 19234151
references.citation: Genes Dev. 2007 Aug 15;21(16):1999-2004
references.pmid: 17626790
references.citation: PLoS One. 2009 Jul 20;4(7):e6309
references.pmid: 19617918
references.citation: Nat Genet. 2003 Nov;35(3):215-7
references.pmid: 14528307
references.citation: J Exp Med. 2008 Mar 17;205(3):565-74
references.pmid: 18283119
references.citation: Nature. 2009 Sep 24;461(7263):546-9
references.pmid: 19734881
references.citation: Cell. 2005 Dec 16;123(6):1133-46
references.pmid: 16337999
references.citation: Nat Genet. 2003 Nov;35(3):217-8
references.pmid: 14528306
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Nature. 2008 Apr 17;452(7189):896-9
references.pmid: 18368051
references.citation: Nat Rev Immunol. 2002 Apr;2(4):251-62
references.pmid: 12001996
references.citation: Nature. 2008 Sep 4;455(7209):64-71
references.pmid: 18668037
references.citation: Science. 1985 Jul 26;229(4711):345-52
references.pmid: 2990048
references.citation: Nature. 2008 Oct 30;455(7217):1193-7
references.pmid: 18830242
references.citation: Trends Immunol. 2008 Jul;29(7):343-51
references.pmid: 18515182
references.citation: Curr Biol. 2010 Feb 23;20(4):367-73
references.pmid: 20096582
references.citation: Nature. 2008 Jun 5;453(7196):803-6
references.pmid: 18463630
references.citation: Genes Dev. 2005 Feb 15;19(4):489-501
references.pmid: 15713842
references.citation: Genes Dev. 2008 Oct 15;22(20):2773-85
references.pmid: 18923076