title: The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell-mediated peripheral T cell unresponsiveness.
abstract: Induced regulatory T cells (iT(reg) cells) can be generated by peripheral dendritic cells (DCs) that mediate T cell unresponsiveness to rechallenge with antigen. The molecular factors required for the function of such iT(reg) cells remain unknown. We report a critical role for the transcription cofactor homeodomain-only protein (Hop; also known as Hopx) in iT(reg) cells to mediate T cell unresponsiveness in vivo. Hopx-sufficient iT(reg) cells downregulated expression of the transcription factor AP-1 complex and suppressed other T cells. In the absence of Hopx, iT(reg) cells had high expression of the AP-1 complex, proliferated and failed to mediate T cell unresponsiveness to rechallenge with antigen. Thus, Hopx is required for the function of T(reg) cells induced by DCs and the promotion of DC-mediated T cell unresponsiveness in vivo.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hawiger
authors.forename: Yisong Y
authors.initials: YY
authors.lastname: Wan
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Eynon
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C466740:Hop protein, mouse; D018808:Transcription Factor AP-1
references.citation: J Immunol. 1999 May 1;162(9):5317-26
references.pmid: 10228007
references.citation: Nat Immunol. 2002 Jan;3(1):33-41
references.pmid: 11740498
references.citation: Nat Immunol. 2007 Mar;8(3):277-84
references.pmid: 17220892
references.citation: Nature. 2007 Feb 15;445(7129):771-5
references.pmid: 17220874
references.citation: Cell. 2002 Sep 20;110(6):713-23
references.pmid: 12297045
references.citation: Genes Dev. 2009 Jun 1;23(11):1270-82
references.pmid: 19487568
references.citation: J Exp Med. 2001 Sep 17;194(6):769-79
references.pmid: 11560993
references.citation: Eur J Immunol. 2008 Apr;38(4):908-11
references.pmid: 18395857
references.citation: Science. 1992 Aug 21;257(5073):1134-8
references.pmid: 1509265
references.citation: Nat Immunol. 2009 Jul;10(7):689-95
references.pmid: 19536194
references.citation: Cell. 2006 Jul 28;126(2):375-87
references.pmid: 16873067
references.citation: Annu Rev Immunol. 2009;27:287-312
references.pmid: 19302042
references.citation: Nat Immunol. 2005 Dec;6(12):1219-27
references.pmid: 16244650
references.citation: J Exp Med. 2007 Jun 11;204(6):1257-65
references.pmid: 17502665
references.citation: Nature. 2007 Feb 22;445(7130):936-40
references.pmid: 17237761
references.citation: Immunol Cell Biol. 1998 Feb;76(1):34-40
references.pmid: 9553774
references.citation: J Biol Chem. 2007 Mar 9;282(10):7700-9
references.pmid: 17192267
references.citation: Annu Rev Immunol. 2003;21:685-711
references.pmid: 12615891
references.citation: Nat Immunol. 2010 Jan;11(1):7-13
references.pmid: 20016504
references.citation: Proc Natl Acad Sci U S A. 1978 Oct;75(10):5132-6
references.pmid: 154105
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8886-91
references.pmid: 12857946
references.citation: J Exp Med. 1979 Jan 1;149(1):1-16
references.pmid: 762493
references.citation: J Exp Med. 1975 Apr 1;141(4):804-20
references.pmid: 1127378
references.citation: Immunity. 2008 Jul 18;29(1):114-26
references.pmid: 18617425
references.citation: J Immunol. 2008 Nov 15;181(10):6923-33
references.pmid: 18981112
references.citation: Nat Immunol. 2002 Aug;3(8):756-63
references.pmid: 12089509
references.citation: J Exp Med. 2007 Aug 6;204(8):1775-85
references.pmid: 17620362
references.citation: Nat Immunol. 2008 Mar;9(3):239-44
references.pmid: 18285775
references.citation: Nat Immunol. 2003 Apr;4(4):330-6
references.pmid: 12612578
references.citation: Curr Opin Immunol. 1997 Jun;9(3):351-7
references.pmid: 9203408
references.citation: Nat Immunol. 2005 Apr;6(4):327-30
references.pmid: 15785757
references.citation: Immunity. 2004 Jun;20(6):695-705
references.pmid: 15189735
references.citation: Nat Genet. 2001 Jan;27(1):68-73
references.pmid: 11138001
references.citation: Immunity. 2007 Nov;27(5):786-800
references.pmid: 18024188
references.citation: Cell. 1988 Dec 23;55(6):989-1003
references.pmid: 3203386
references.citation: J Exp Med. 2003 Sep 1;198(5):737-46
references.pmid: 12939344
references.citation: Cell. 2002 Sep 20;110(6):725-35
references.pmid: 12297046
references.citation: Int Immunol. 2006 Aug;18(8):1197-209
references.pmid: 16772372
references.citation: Blood. 2008 Apr 1;111(7):3599-606
references.pmid: 18223166
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 Aug;291(2):L191-9
references.pmid: 16510470
references.citation: Oncogene. 2001 Apr 30;20(19):2390-400
references.pmid: 11402335
references.citation: Nature. 2007 Sep 20;449(7160):361-5
references.pmid: 17694047
references.citation: Immunol Rev. 2003 Feb;191:62-78
references.pmid: 12614352
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5126-31
references.pmid: 15795373
references.citation: Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):979-84
references.pmid: 8577772
references.citation: J Exp Med. 2007 Aug 6;204(8):1757-64
references.pmid: 17620361
references.citation: Annu Rev Immunol. 2004;22:531-62
references.pmid: 15032588
references.citation: Immunol Rev. 2006 Aug;212:163-9
references.pmid: 16903913