title: TGF-beta and regulatory T cell in immunity and autoimmunity.
abstract: BACKGROUND
  The immune response is controlled by several inhibitory mechanisms. These mechanisms include regulatory T cells, which exist in multiple classes. Notable among these are Foxp3-expressing regulatory T cells (Treg), NKT cells, and Tr1 cells. Common to these mechanisms are inhibitory cytokines such as interleukin-10 and transforming growth factor-beta (TGF-beta). TGF-beta and Foxp3-expressing Treg cells are critical in maintaining self-tolerance and immune homeostasis.
  
  
  CONCLUSIONS
  The immune suppressive functions of TGF-beta and Treg cells are widely acknowledged and extensively studied. Nonetheless, recent studies revealed the positive roles for TGF-beta and Treg cells in shaping the immune system and the inflammatory responses. In this paper, we will discuss the role of these mechanisms in the control of immunity and autoimmunity and the mechanisms that underlie how these molecules control these responses.
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, School of Medicine, CB 7295, 450 West Drive, Chapel Hill, North Carolina, NC 27599-7295, USA. wany@email.unc.edu
authors.forename: Yisong Y
authors.initials: YY
authors.lastname: Wan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D015551:Autoimmunity; D016207:Cytokines / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007109:Immunity; D051379:Mice; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta
references.citation: J Immunol. 2004 May 15;172(10):5986-93
references.pmid: 15128781
references.citation: J Cell Sci. 2003 Jan 15;116(Pt 2):217-24
references.pmid: 12482908
references.citation: Immunity. 2002 Jan;16(1):23-35
references.pmid: 11825563
references.citation: J Exp Med. 1994 Nov 1;180(5):1937-42
references.pmid: 7964469
references.citation: Nature. 2003 Oct 9;425(6958):577-84
references.pmid: 14534577
references.citation: Nature. 2006 May 11;441(7090):235-8
references.pmid: 16648838
references.citation: J Immunol. 1991 May 15;146(10):3289-97
references.pmid: 1827481
references.citation: Immunity. 2006 Feb;24(2):179-89
references.pmid: 16473830
references.citation: J Immunol. 2005 May 15;174(10):5950-8
references.pmid: 15879087
references.citation: Mol Cell. 1998 Mar;1(4):611-7
references.pmid: 9660945
references.citation: J Biol Chem. 1999 Dec 24;274(52):37413-20
references.pmid: 10601313
references.citation: J Immunol. 2004 May 1;172(9):5149-53
references.pmid: 15100250
references.citation: Genes Dev. 1999 Apr 1;13(7):804-16
references.pmid: 10197981
references.citation: Nat Immunol. 2005 Dec;6(12):1219-27
references.pmid: 16244650
references.citation: Nat Immunol. 2003 Apr;4(4):337-42
references.pmid: 12612581
references.citation: J Immunol. 1994 Oct 15;153(8):3514-22
references.pmid: 7930573
references.citation: Nature. 2007 Feb 22;445(7130):936-40
references.pmid: 17237761
references.citation: Science. 2003 Feb 14;299(5609):1057-61
references.pmid: 12522256
references.citation: Nat Immunol. 2005 Jun;6(6):600-7
references.pmid: 15852008
references.citation: Nat Genet. 2001 Jan;27(1):20-1
references.pmid: 11137993
references.citation: J Exp Med. 2005 Oct 3;202(7):901-6
references.pmid: 16203863
references.citation: J Exp Med. 1998 Jul 20;188(2):287-96
references.pmid: 9670041
references.citation: J Exp Med. 1987 Oct 1;166(4):991-8
references.pmid: 3498791
references.citation: J Biol Chem. 1998 Nov 20;273(47):31455-62
references.pmid: 9813058
references.citation: J Exp Med. 2003 Oct 20;198(8):1179-88
references.pmid: 14557415
references.citation: Nat Immunol. 2005 Nov;6(11):1133-41
references.pmid: 16200068
references.citation: Mol Cell Biol. 1993 Feb;13(2):1155-62
references.pmid: 8423782
references.citation: Eur J Immunol. 2004 Sep;34(9):2480-8
references.pmid: 15307180
references.citation: Cancer Cell. 2005 Nov;8(5):369-80
references.pmid: 16286245
references.citation: J Exp Med. 2003 Jun 16;197(12):1689-99
references.pmid: 12810687
references.citation: Eur J Immunol. 2000 Jul;30(7):2101-11
references.pmid: 10940900
references.citation: J Exp Med. 1982 Dec 1;156(6):1565-76
references.pmid: 6983557
references.citation: Nature. 1992 Oct 22;359(6397):693-9
references.pmid: 1436033
references.citation: Immunity. 2006 Jun;24(6):677-688
references.pmid: 16782025
references.citation: Annu Rev Immunol. 1998;16:137-61
references.pmid: 9597127
references.citation: J Exp Med. 2002 Jun 3;195(11):1499-505
references.pmid: 12045248
references.citation: Nat Immunol. 2005 Apr;6(4):345-52
references.pmid: 15785760
references.citation: J Allergy Clin Immunol. 2007 Oct;120(4):744-50; quiz 751-2
references.pmid: 17931557
references.citation: Immunity. 2007 May;26(5):579-91
references.pmid: 17481928
references.citation: Nat Rev Immunol. 2002 Jun;2(6):389-400
references.pmid: 12093005
references.citation: Nat Immunol. 2005 Nov;6(11):1152-9
references.pmid: 16227983
references.citation: Blood. 2005 Jan 15;105(2):735-41
references.pmid: 15454488
references.citation: J Immunol. 1993 Jul 15;151(2):668-77
references.pmid: 8335902
references.citation: EMBO J. 1999 Mar 1;18(5):1280-91
references.pmid: 10064594
references.citation: Mol Cell. 2001 Sep;8(3):671-82
references.pmid: 11583628
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Mar;284(3):G525-35
references.pmid: 12466145
references.citation: Immunol Rev. 2001 Aug;182:207-14
references.pmid: 11722636
references.citation: J Biol Chem. 2001 Sep 7;276(36):33986-94
references.pmid: 11448947
references.citation: Nat Immunol. 2003 Apr;4(4):330-6
references.pmid: 12612578
references.citation: Nat Immunol. 2005 Apr;6(4):327-30
references.pmid: 15785757
references.citation: J Cell Biol. 2004 Jun 7;165(5):723-34
references.pmid: 15184403
references.citation: Nat Immunol. 2007 May;8(5):457-62
references.pmid: 17440451
references.citation: Annu Rev Immunol. 2000;18:423-49
references.pmid: 10837065
references.citation: J Neurosci Res. 2005 Jul 1;81(1):45-52
references.pmid: 15952173
references.citation: Blood. 2002 Jul 15;100(2):560-8
references.pmid: 12091349
references.citation: Blood. 2004 Jun 15;103(12):4594-601
references.pmid: 15016653
references.citation: J Exp Med. 2001 Aug 20;194(4):439-53
references.pmid: 11514601
references.citation: Novartis Found Symp. 2003;252:55-63; discussion 63-6, 106-14
references.pmid: 14609212
references.citation: Nat Immunol. 2001 Dec;2(12):1174-82
references.pmid: 11694881
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4572-7
references.pmid: 15070759
references.citation: Immunity. 2000 Oct;13(4):443-51
references.pmid: 11070163
references.citation: Nat Genet. 2001 Jan;27(1):68-73
references.pmid: 11138001
references.citation: Eur J Immunol. 2000 Sep;30(9):2639-49
references.pmid: 11009098
references.citation: Blood. 2004 Oct 1;104(7):2187-93
references.pmid: 15172973
references.citation: Immunology. 2001 Mar;102(3):310-6
references.pmid: 11298829
references.citation: J Immunol. 2000 Nov 1;165(9):4773-7
references.pmid: 11045997
references.citation: J Immunol. 1986 Dec 15;137(12):3855-60
references.pmid: 2878044
references.citation: Mol Cell. 2002 Aug;10(2):283-94
references.pmid: 12191474
references.citation: Cell. 1998 Sep 4;94(5):585-94
references.pmid: 9741623
references.citation: Nature. 2006 May 11;441(7090):231-4
references.pmid: 16648837
references.citation: J Exp Med. 1986 May 1;163(5):1037-50
references.pmid: 2871125
references.citation: Immunity. 2007 Nov;27(5):786-800
references.pmid: 18024188
references.citation: Immunology. 1971 Dec;21(6):903-14
references.pmid: 4943147
references.citation: Immunol Rev. 2005 Aug;206:232-59
references.pmid: 16048553
references.citation: Annu Rev Immunol. 2005;23:515-48
references.pmid: 15771580
references.citation: Nat Genet. 2001 Jan;27(1):18-20
references.pmid: 11137992
references.citation: J Biol Chem. 1999 Jul 16;274(29):20709-16
references.pmid: 10400705
references.citation: Nat Immunol. 2007 Mar;8(3):277-84
references.pmid: 17220892
references.citation: J Immunol. 1995 Jul 15;155(2):609-18
references.pmid: 7608539
references.citation: J Immunol. 2004 Apr 1;172(7):4275-84
references.pmid: 15034041
references.citation: Nat Immunol. 2007 Feb;8(2):191-7
references.pmid: 17136045
references.citation: Nature. 1997 Oct 16;389(6652):737-42
references.pmid: 9338786
references.citation: Nature. 2007 Feb 15;445(7129):771-5
references.pmid: 17220874
references.citation: J Immunol. 2001 Jun 15;166(12):7282-9
references.pmid: 11390478
references.citation: J Immunol. 2005 May 1;174(9):5215-23
references.pmid: 15843517
references.citation: J Exp Med. 1999 Jan 18;189(2):231-9
references.pmid: 9892606
references.citation: Scand J Immunol. 1999 Dec;50(6):612-8
references.pmid: 10607309
references.citation: Am J Pathol. 1999 Sep;155(3):841-51
references.pmid: 10487979
references.citation: Cell. 1999 Feb 5;96(3):319-28
references.pmid: 10025398
references.citation: J Exp Med. 2006 Oct 2;203(10):2271-9
references.pmid: 16982811
references.citation: J Immunol. 2004 Dec 1;173(11):6526-31
references.pmid: 15557141
references.citation: Immunity. 2000 Feb;12(2):171-81
references.pmid: 10714683
references.citation: J Exp Med. 2007 Mar 19;204(3):475-80
references.pmid: 17353370
references.citation: Nature. 2007 Feb 15;445(7129):766-70
references.pmid: 17220876
references.citation: J Exp Med. 2005 Mar 7;201(5):737-46
references.pmid: 15753207
references.citation: J Exp Med. 2000 Apr 3;191(7):1187-96
references.pmid: 10748236
references.citation: J Clin Invest. 1996 Nov 1;98(9):2109-19
references.pmid: 8903331
references.citation: Nat Rev Immunol. 2002 Dec;2(12):933-44
references.pmid: 12461566
references.citation: Nat Immunol. 2007 Dec;8(12):1353-62
references.pmid: 17982458
references.citation: Immunity. 2006 Sep;25(3):455-71
references.pmid: 16973386
references.citation: Transplant Rev. 1975;26:170-85
references.pmid: 1101469
references.citation: Eur J Immunol. 2004 May;34(5):1303-11
references.pmid: 15114663
references.citation: Cell. 1998 Jun 26;93(7):1159-70
references.pmid: 9657149
references.citation: Annu Rev Immunol. 1989;7:145-73
references.pmid: 2523712
references.citation: Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4
references.pmid: 8421714
references.citation: Blood. 2006 Jul 1;108(1):253-61
references.pmid: 16537805
references.citation: Immunity. 2006 Dec;25(6):941-52
references.pmid: 17137799
references.citation: J Immunol. 2006 Nov 1;177(9):5852-60
references.pmid: 17056509
references.citation: Immunol Res. 1999;19(1):1-24
references.pmid: 10374692
references.citation: J Exp Med. 2000 Jul 17;192(2):151-8
references.pmid: 10899902
references.citation: Mol Cell Biol. 1999 Apr;19(4):2495-504
references.pmid: 10082515
references.citation: Nat Immunol. 2006 Nov;7(11):1151-6
references.pmid: 16998492
references.citation: J Exp Med. 2005 Apr 4;201(7):1061-7
references.pmid: 15809351
references.citation: J Exp Med. 1982 Dec 1;156(6):1577-86
references.pmid: 6983558
references.citation: J Exp Med. 2003 Dec 15;198(12):1875-86
references.pmid: 14676299
references.citation: J Immunol. 1995 Aug 1;155(3):1151-64
references.pmid: 7636184
references.citation: Nat Rev Immunol. 2002 Jan;2(1):46-53
references.pmid: 11905837
references.citation: Biochemistry. 2002 Jan 15;41(2):579-87
references.pmid: 11781097
references.citation: Immunity. 2006 Sep;25(3):441-54
references.pmid: 16973387
references.citation: Cell. 2000 Mar 17;100(6):655-69
references.pmid: 10761931
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5126-31
references.pmid: 15795373
references.citation: J Exp Med. 2006 Mar 20;203(3):505-11
references.pmid: 16533880
references.citation: J Exp Med. 2002 Sep 16;196(6):851-7
references.pmid: 12235217
references.citation: Cell Immunol. 2000 Aug 25;204(1):46-54
references.pmid: 11006017
references.citation: J Immunol. 2006 Oct 1;177(7):4376-83
references.pmid: 16982872
references.citation: Int Immunol. 2005 Mar;17(3):279-88
references.pmid: 15684039
references.citation: Annu Rev Biochem. 1998;67:753-91
references.pmid: 9759503
references.citation: Nat Immunol. 2005 Nov;6(11):1142-51
references.pmid: 16227984
references.citation: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2433-7
references.pmid: 2320565
references.citation: Nat Med. 2001 Oct;7(10):1118-22
references.pmid: 11590434
references.citation: N Engl J Med. 2000 May 4;342(18):1350-8
references.pmid: 10793168
references.citation: EMBO J. 2002 Jul 15;21(14):3749-59
references.pmid: 12110587
references.citation: J Immunol. 2006 Apr 15;176(8):4748-56
references.pmid: 16585568
references.citation: J Exp Med. 2001 Sep 3;194(5):629-44
references.pmid: 11535631
references.citation: J Immunol. 2003 May 1;170(9):4785-92
references.pmid: 12707360
references.citation: J Exp Med. 1999 Oct 4;190(7):995-1004
references.pmid: 10510089
references.citation: Immunity. 2005 Mar;22(3):329-41
references.pmid: 15780990
references.citation: J Exp Med. 2000 Jul 17;192(2):303-10
references.pmid: 10899917
references.citation: Immunol Lett. 2001 Sep 3;78(2):83-8
references.pmid: 11672591
references.citation: Annu Rev Immunol. 2004;22:531-62
references.pmid: 15032588
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10878-83
references.pmid: 12949259
references.citation: Immunol Rev. 2001 Aug;182:68-79
references.pmid: 11722624
references.citation: Immunology. 1970 May;18(5):723-37
references.pmid: 4911896
references.citation: Annu Rev Immunol. 2006;24:99-146
references.pmid: 16551245
references.citation: J Exp Med. 2005 Oct 17;202(8):1141-51
references.pmid: 16230479
references.citation: Nat Immunol. 2003 Dec;4(12):1206-12
references.pmid: 14578884
references.citation: Mol Cell Biol. 1998 Nov;18(11):6595-604
references.pmid: 9774674
references.citation: J Immunol. 1998 Aug 15;161(4):1664-70
references.pmid: 9712029
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):419-24
references.pmid: 15623559
references.citation: J Biol Chem. 2002 Nov 1;277(44):41361-8
references.pmid: 12193595
references.citation: Immunity. 2006 Jul;25(1):129-41
references.pmid: 16860762