title: Regulatory T cells in nonlymphoid tissues.
abstract: Both Foxp3(+)CD4(+) regulatory T cells (Treg cells) and local immune responses in nonlymphoid tissues have long been recognized as important elements of a well-orchestrated immune system, but only recently have these two fields of study begun to intersect. There is growing evidence that Treg cells are present in various nonlymphoid tissues in health and disease, that they have a unique phenotype and that their functions go beyond the classical modulation of immune responses. Thus, tissue Treg cells might add yet another level to classification of the Treg cell compartment into functional and/or phenotypic subtypes. In this Review, we summarize recent findings in this new field, discussing knowns and unknowns about the origin, phenotype, function and memory of nonlymphoid tissue-resident Treg cells.
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Dalia
authors.initials: D
authors.lastname: Burzyn
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
mesh_terms: D000818:Animals; D006801:Humans; D007156:Immunologic Memory; D009928:Organ Specificity / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
references.citation: Nature. 2012 Feb 08;482(7385):395-9
references.pmid: 22318520
references.citation: J Clin Invest. 2008 Nov;118(11):3639-50
references.pmid: 18924611
references.citation: Science. 2009 Nov 13;326(5955):986-91
references.pmid: 19797626
references.citation: Cancer Microenviron. 2013 Aug;6(2):147-57
references.pmid: 23104434
references.citation: Nature. 2012 Oct 4;490(7418):102-6
references.pmid: 23023128
references.citation: Nat Rev Immunol. 2013 Jan;13(1):23-33
references.pmid: 23237963
references.citation: J Immunol. 2007 Feb 15;178(4):2155-62
references.pmid: 17277120
references.citation: Cell. 2010 Mar 19;140(6):883-99
references.pmid: 20303878
references.citation: Blood. 2013 Jan 24;121(4):679-91
references.pmid: 23160472
references.citation: Nat Immunol. 2009 Jul;10(7):689-95
references.pmid: 19536194
references.citation: J Exp Med. 2005 Apr 4;201(7):1037-44
references.pmid: 15809349
references.citation: PLoS One. 2007 Aug 22;2(8):e779
references.pmid: 17712427
references.citation: Nature. 2006 Dec 14;444(7121):860-7
references.pmid: 17167474
references.citation: Annu Rev Immunol. 2012;30:531-64
references.pmid: 22224781
references.citation: Cancer Res. 2009 Mar 1;69(5):2000-9
references.pmid: 19244125
references.citation: Nat Med. 2009 Aug;15(8):930-9
references.pmid: 19633656
references.citation: Annu Rev Immunol. 2012;30:733-58
references.pmid: 22224762
references.citation: PLoS One. 2010 Oct 26;5(10):e13623
references.pmid: 21049016
references.citation: J Immunol. 2008 Apr 15;180(8):5737-45
references.pmid: 18390759
references.citation: Immunity. 2012 May 25;36(5):873-84
references.pmid: 22560445
references.citation: Nature. 2009 Mar 19;458(7236):351-6
references.pmid: 19182775
references.citation: Nat Med. 2006 May;12(5):518-25
references.pmid: 16633347
references.citation: Immunity. 2013 Jan 24;38(1):79-91
references.pmid: 23273845
references.citation: J Clin Oncol. 2006 Dec 1;24(34):5373-80
references.pmid: 17135638
references.citation: Blood. 2007 Jan 1;109(1):194-202
references.pmid: 16968902
references.citation: Nature. 2011 Feb 24;470(7335):548-53
references.pmid: 21326202
references.citation: Nat Med. 2011 Jul 24;17(8):983-8
references.pmid: 21785430
references.citation: J Exp Med. 2013 Apr 8;210(4):775-88
references.pmid: 23547101
references.citation: Nat Med. 2006 Feb;12(2):178-80
references.pmid: 16462800
references.citation: Nat Med. 2009 Feb;15(2):192-9
references.pmid: 19169263
references.citation: Eur J Cancer. 2008 Sep;44(13):1875-82
references.pmid: 18617393
references.citation: J Immunol. 2007 Mar 1;178(5):2883-92
references.pmid: 17312132
references.citation: J Exp Med. 2006 Mar 20;203(3):777-88
references.pmid: 16533885
references.citation: J Exp Med. 2007 Aug 6;204(8):1775-85
references.pmid: 17620362
references.citation: Nat Rev Immunol. 2011 Feb;11(2):119-30
references.pmid: 21267013
references.citation: J Exp Med. 2007 Jun 11;204(6):1335-47
references.pmid: 17548521
references.citation: Science. 2013 Mar 8;339(6124):1219-24
references.pmid: 23471412
references.citation: Nature. 2010 Feb 11;463(7282):808-12
references.pmid: 20072126
references.citation: Nature. 2011 Nov 27;480(7378):538-42
references.pmid: 22121024
references.citation: Cell Immunol. 2012 Jul-Aug;278(1-2):76-83
references.pmid: 23121978
references.citation: PLoS One. 2011 Jan 26;6(1):e16376
references.pmid: 21298111
references.citation: Arthritis Rheum. 2007 Feb;56(2):509-20
references.pmid: 17265486
references.citation: Immunity. 2009 Mar 20;30(3):458-69
references.pmid: 19303390
references.citation: Am J Reprod Immunol. 2013 Apr;69(4):359-68
references.pmid: 23405982
references.citation: J Immunol. 2009 Feb 1;182(3):1746-55
references.pmid: 19155524
references.citation: Immunity. 2012 May 25;36(5):731-41
references.pmid: 22579475
references.citation: Nature. 2011 Jul 13;475(7355):226-30
references.pmid: 21753853
references.citation: Carcinogenesis. 2009 Jul;30(7):1073-81
references.pmid: 19468060
references.citation: J Exp Med. 2008 Sep 1;205(9):2125-38
references.pmid: 18725522
references.citation: J Immunol. 2009 Mar 15;182(6):3461-8
references.pmid: 19265124
references.citation: J Exp Med. 2004 Jun 7;199(11):1479-89
references.pmid: 15184501
references.citation: Annu Rev Biochem. 2008;77:289-312
references.pmid: 18518822
references.citation: Immunity. 2012 Sep 21;37(3):511-23
references.pmid: 22981537
references.citation: Nat Med. 2004 Sep;10(9):942-9
references.pmid: 15322536
references.citation: Nat Immunol. 2009 Jun;10(6):595-602
references.pmid: 19412181
references.citation: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9765-70
references.pmid: 20445103
references.citation: Science. 1993 Jan 1;259(5091):87-91
references.pmid: 7678183
references.citation: J Clin Invest. 2013 Mar;123(3):1323-34
references.pmid: 23426179
references.citation: Mol Med. 2012 May 09;18:598-605
references.pmid: 22331026
references.citation: Nature. 2012 Jun 28;486(7404):549-53
references.pmid: 22722857
references.citation: Basic Res Cardiol. 2012 Jan;107(1):232
references.pmid: 22189560
references.citation: Immunity. 2012 Sep 21;37(3):501-10
references.pmid: 22960221
references.citation: Science. 2011 Jan 21;331(6015):337-41
references.pmid: 21205640
references.citation: Trends Immunol. 2013 Jan;34(1):33-40
references.pmid: 22999714
references.citation: Trends Immunol. 2013 Feb;34(2):74-80
references.pmid: 23219401
references.citation: Diabetes. 2011 Nov;60(11):2954-62
references.pmid: 21911743
references.citation: J Immunol. 2011 Aug 1;187(3):1150-6
references.pmid: 21697460
references.citation: Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4345-54
references.pmid: 17671115
references.citation: J Immunol. 2013 Apr 1;190(7):3438-46
references.pmid: 23467933
references.citation: Cell. 2012 Jul 6;150(1):29-38
references.pmid: 22770213
references.citation: Clin Cancer Res. 2012 Jun 1;18(11):3022-9
references.pmid: 22510350
references.citation: J Immunol. 2009 Oct 1;183(7):4360-70
references.pmid: 19734224
references.citation: J Exp Med. 2007 Aug 6;204(8):1757-64
references.pmid: 17620361
references.citation: J Immunol. 2010 Apr 1;184(7):3433-41
references.pmid: 20181882
references.citation: PLoS One. 2012;7(2):e30676
references.pmid: 22363469
references.citation: Nat Med. 2011 Jul 24;17(8):975-82
references.pmid: 21785433
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):594-9
references.pmid: 17197426
references.citation: Cancer Immunol Immunother. 2011 Jul;60(7):909-18
references.pmid: 21644034
references.citation: Trends Immunol. 2012 Apr;33(4):174-80
references.pmid: 22305714
references.citation: J Immunol. 2012 Sep 15;189(6):2805-14
references.pmid: 22855712