title: Cellular and molecular basis for the regulation of inflammation by TGF-beta.
abstract: Transforming growth factor-beta (TGF-beta) has been shown to play an essential role in the suppression of inflammation, yet recent studies have revealed the positive roles of TGF-beta in inflammatory responses. For example, TGF-beta induces Foxp3-positive regulatory T cells (iTregs) in the presence of interleukin-2 (IL-2), while in the presence of IL-6, it induces pathogenic IL-17 producing Th17 cells. TGF-beta inhibits the proliferation of immune cells as well as cytokine production via Foxp3-dependent and -independent mechanisms. Little is known about molecular mechanisms involved in immune suppression via TGF-beta; however, Smad2/3 have been shown to play essential roles in Foxp3 induction as well as in IL-2 and IFN-gamma suppression, whereas Th17 differentiation is promoted via the Smad-independent pathway. Interaction between TGF-beta and other cytokine signaling is important in establishing the balance of immunity and tolerance.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. yoshimura@a6.keio.jp
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Yu
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Mori
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D051896:Smad Proteins, Receptor-Regulated / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D051896:Smad Proteins, Receptor-Regulated; D016212:Transforming Growth Factor beta
references.citation: Nat Rev Immunol. 2008 May;8(5):337-48
references.pmid: 18408735
references.citation: Immunity. 2007 May;26(5):579-91
references.pmid: 17481928
references.citation: Microbes Infect. 1999 Dec;1(15):1283-90
references.pmid: 10611756
references.citation: Blood. 1999 Feb 15;93(4):1208-20
references.pmid: 9949163
references.citation: Nature. 2008 Sep 11;455(7210):246-50
references.pmid: 18701887
references.citation: J Cell Sci. 2003 Jan 15;116(Pt 2):217-24
references.pmid: 12482908
references.citation: Nat Immunol. 2008 Dec;9(12):1341-6
references.pmid: 18931678
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: Blood. 2008 Sep 1;112(5):1813-21
references.pmid: 18550850
references.citation: Immunity. 2006 Feb;24(2):179-89
references.pmid: 16473830
references.citation: Cell Immunol. 2004 Nov-Dec;232(1-2):96-104
references.pmid: 15922720
references.citation: Nat Immunol. 2005 Jun;6(6):600-7
references.pmid: 15852008
references.citation: J Clin Invest. 1998 Feb 15;101(4):890-8
references.pmid: 9466984
references.citation: Cell. 2008 Aug 8;134(3):392-404
references.pmid: 18692464
references.citation: J Immunol. 2008 Oct 15;181(8):5194-8
references.pmid: 18832670
references.citation: Genes Cells. 2006 Aug;11(8):871-82
references.pmid: 16866871
references.citation: J Immunol. 1999 Nov 1;163(9):4869-77
references.pmid: 10528188
references.citation: Nat Immunol. 2005 Nov;6(11):1133-41
references.pmid: 16200068
references.citation: J Biol Chem. 2007 Mar 30;282(13):9358-9363
references.pmid: 17277312
references.citation: Mol Cell Biol. 1993 Feb;13(2):1155-62
references.pmid: 8423782
references.citation: Immunity. 2008 Jul 18;29(1):44-56
references.pmid: 18585065
references.citation: J Immunol. 2006 May 1;176(9):5652-61
references.pmid: 16622035
references.citation: J Immunol. 1990 Mar 1;144(5):1767-76
references.pmid: 2407783
references.citation: FASEB J. 2001 Mar;15(3):797-806
references.pmid: 11259398
references.citation: J Biol Chem. 2008 Jun 20;283(25):17003-8
references.pmid: 18434325
references.citation: Nature. 1992 Oct 22;359(6397):693-9
references.pmid: 1436033
references.citation: Science. 2009 Nov 13;326(5955):986-91
references.pmid: 19797626
references.citation: Proc Natl Acad Sci U S A. 2006 May 23;103(21):8137-42
references.pmid: 16698929
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20846-51
references.pmid: 19088203
references.citation: J Exp Med. 2002 Jun 3;195(11):1499-505
references.pmid: 12045248
references.citation: J Immunol. 2008 Nov 15;181(10):6923-33
references.pmid: 18981112
references.citation: Eur J Immunol. 2000 Jul;30(7):2101-11
references.pmid: 10940900
references.citation: Nature. 1998 Jun 25;393(6687):786-90
references.pmid: 9655392
references.citation: Nature. 1994 Sep 15;371(6494):257-61
references.pmid: 8078588
references.citation: J Immunol. 2001 Jul 15;167(2):773-8
references.pmid: 11441082
references.citation: Nitric Oxide. 2005 Aug;13(1):78-87
references.pmid: 15964225
references.citation: J Exp Med. 2005 Jan 17;201(2):233-40
references.pmid: 15657292
references.citation: Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12215-9
references.pmid: 8618872
references.citation: EMBO J. 1999 Mar 1;18(5):1280-91
references.pmid: 10064594
references.citation: Cell. 2006 Jun 2;125(5):929-41
references.pmid: 16751102
references.citation: Mol Cell. 2001 Sep;8(3):671-82
references.pmid: 11583628
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2758-63
references.pmid: 16473944
references.citation: Nat Rev Immunol. 2007 Jun;7(6):443-53
references.pmid: 17525753
references.citation: Nat Immunol. 2003 Apr;4(4):330-6
references.pmid: 12612578
references.citation: Nature. 2010 Feb 11;463(7282):808-12
references.pmid: 20072126
references.citation: J Leukoc Biol. 2009 Jan;85(1):29-33
references.pmid: 18818372
references.citation: J Immunol. 2007 Aug 15;179(4):2170-9
references.pmid: 17675476
references.citation: J Immunol. 2007 Jan 1;178(1):280-90
references.pmid: 17182565
references.citation: J Immunol. 1996 Aug 15;157(4):1499-507
references.pmid: 8759731
references.citation: Nat Immunol. 2008 Feb;9(2):194-202
references.pmid: 18157133
references.citation: Pharmacol Ther. 2003 May;98(2):257-65
references.pmid: 12725873
references.citation: Nat Immunol. 2001 Dec;2(12):1174-82
references.pmid: 11694881
references.citation: J Biol Chem. 2003 Jan 17;278(3):1910-4
references.pmid: 12417590
references.citation: Eur J Immunol. 2000 Sep;30(9):2639-49
references.pmid: 11009098
references.citation: Eur J Immunol. 2009 May;39(5):1241-51
references.pmid: 19337996
references.citation: J Exp Med. 2008 Jul 7;205(7):1543-50
references.pmid: 18591412
references.citation: J Immunol. 2005 Mar 1;174(5):2720-9
references.pmid: 15728480
references.citation: Int Immunol. 2008 Jun;20(6):753-62
references.pmid: 18381351
references.citation: J Immunol. 2007 Apr 1;178(7):4284-95
references.pmid: 17371985
references.citation: Endocr Rev. 2002 Dec;23(6):787-823
references.pmid: 12466190
references.citation: J Immunol. 2000 Nov 1;165(9):4773-7
references.pmid: 11045997
references.citation: J Exp Med. 2006 Apr 17;203(4):1021-31
references.pmid: 16606674
references.citation: Nature. 2006 May 11;441(7090):231-4
references.pmid: 16648837
references.citation: Immunity. 2008 Apr;28(4):468-76
references.pmid: 18400189
references.citation: J Immunol. 1990 Aug 1;145(3):940-4
references.pmid: 2115549
references.citation: J Immunol. 2000 Dec 1;165(11):6107-15
references.pmid: 11086043
references.citation: J Immunol. 2004 Apr 1;172(7):4275-84
references.pmid: 15034041
references.citation: Nat Immunol. 2003 Dec;4(12):1169-76
references.pmid: 14639467
references.citation: Annu Rev Immunol. 2001;19:683-765
references.pmid: 11244051
references.citation: J Biol Chem. 2008 May 30;283(22):14955-62
references.pmid: 18400747
references.citation: J Immunol. 2004 Sep 1;173(5):3093-102
references.pmid: 15322169
references.citation: J Immunol. 2007 Apr 1;178(7):4022-6
references.pmid: 17371955
references.citation: J Immunol. 1991 Mar 15;146(6):1849-57
references.pmid: 1900875
references.citation: J Biol Chem. 2001 Apr 6;276(14):11041-8
references.pmid: 11134049
references.citation: J Immunol. 2009 Jan 15;182(2):1041-9
references.pmid: 19124747
references.citation: Immunity. 2000 Feb;12(2):171-81
references.pmid: 10714683
references.citation: Nature. 2008 Apr 10;452(7188):773-6
references.pmid: 18337720
references.citation: J Clin Invest. 1996 Nov 1;98(9):2109-19
references.pmid: 8903331
references.citation: Science. 2007 Jul 13;317(5835):256-60
references.pmid: 17569825
references.citation: Nature. 1999 Feb 25;397(6721):710-3
references.pmid: 10067896
references.citation: Immunity. 2006 Sep;25(3):455-71
references.pmid: 16973386
references.citation: J Immunol. 2004 Jan 15;172(2):834-42
references.pmid: 14707053
references.citation: J Immunol. 2008 Mar 15;180(6):3746-56
references.pmid: 18322180
references.citation: Nature. 2007 Sep 20;449(7160):361-5
references.pmid: 17694047
references.citation: Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4
references.pmid: 8421714
references.citation: Nature. 2007 Jul 26;448(7152):484-487
references.pmid: 17581588
references.citation: J Immunol. 2005 Nov 1;175(9):5666-74
references.pmid: 16237056
references.citation: J Exp Med. 2009 Oct 26;206(11):2407-16
references.pmid: 19808254
references.citation: Nat Immunol. 2006 Nov;7(11):1151-6
references.pmid: 16998492
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5138-43
references.pmid: 15790681
references.citation: Genes Dev. 1994 Jan;8(1):9-22
references.pmid: 8288131
references.citation: J Exp Med. 2005 Apr 4;201(7):1061-7
references.pmid: 15809351
references.citation: Nat Immunol. 2009 Feb;10(2):167-75
references.pmid: 19098919
references.citation: J Exp Med. 2003 Dec 15;198(12):1875-86
references.pmid: 14676299
references.citation: Immunity. 2006 Sep;25(3):441-54
references.pmid: 16973387
references.citation: Nature. 2008 May 8;453(7192):236-40
references.pmid: 18368049
references.citation: Nature. 2006 Jun 22;441(7096):1015-9
references.pmid: 16791201
references.citation: J Immunol. 2008 Jun 1;180(11):7327-37
references.pmid: 18490732
references.citation: J Immunol. 1999 Apr 15;162(8):4567-75
references.pmid: 10201996
references.citation: Immunol Rev. 2007 Dec;220:199-213
references.pmid: 17979848
references.citation: J Exp Med. 2008 Jul 7;205(7):1551-7
references.pmid: 18591410
references.citation: J Immunol. 2010 Jan 1;184(1):30-4
references.pmid: 19949064
references.citation: J Biol Chem. 2005 Feb 18;280(7):5491-5
references.pmid: 15623538
references.citation: Annu Rev Biochem. 1998;67:753-91
references.pmid: 9759503
references.citation: EMBO J. 2002 Jul 15;21(14):3749-59
references.pmid: 12110587
references.citation: Blood. 2007 May 15;109(10):4368-75
references.pmid: 17227828
references.citation: Oncogene. 2004 May 24;23(24):4232-7
references.pmid: 15156178
references.citation: J Immunol. 2003 May 1;170(9):4785-92
references.pmid: 12707360
references.citation: Annu Rev Immunol. 2004;22:531-62
references.pmid: 15032588
references.citation: J Biol Chem. 2000 Nov 24;275(47):36653-8
references.pmid: 10973958
references.citation: J Cell Sci. 2009 Jan 15;122(Pt 2):227-32
references.pmid: 19118215
references.citation: Annu Rev Immunol. 2006;24:99-146
references.pmid: 16551245
references.citation: Nat Immunol. 2008 Jun;9(6):632-40
references.pmid: 18438410
references.citation: J Immunol. 2010 Jul 15;185(2):842-55
references.pmid: 20548029
references.citation: Nat Rev Immunol. 2007 Jun;7(6):454-65
references.pmid: 17525754
references.citation: Semin Immunol. 2007 Dec;19(6):362-71
references.pmid: 18035554
references.citation: Nature. 2007 Jul 26;448(7152):480-3
references.pmid: 17581589
references.citation: Nat Immunol. 2002 Jun;3(6):549-57
references.pmid: 12006974
references.citation: Cell. 2006 Sep 22;126(6):1121-33
references.pmid: 16990136
references.citation: Immunity. 2006 Jul;25(1):129-41
references.pmid: 16860762
references.citation: Nat Immunol. 2005 Nov;6(11):1123-32
references.pmid: 16200070
references.citation: Genes Dev. 2000 Jul 15;14(14):1693-711
references.pmid: 10898785