Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory responses.
To mount an effective type 1 immune response, type 1 T helper (Th1) cells must produce inflammatory cytokines and simultaneously suppress the expression of antiinflammatory cytokines. How these two processes are coordinately regulated at the molecular level is still unclear. In this paper, we show that the proto-oncogene E26 transformation-specific-1 (Ets-1) is necessary for T-bet to promote interferon-gamma production and that Ets-1 is essential for mounting effective Th1 inflammatory responses in vivo. In addition, Ets-1-deficient Th1 cells also produce a very high level of interleukin 10. Thus, Ets-1 plays a crucial and unique role in the reciprocal regulation of inflammatory and antiinflammatory Th responses.
Grenningloh
Roland
R
Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
Kang
Bok Yun
BY
Ho
I-Cheng
IC
D000818:Animals; D049109:Cell Proliferation; D003092:Colitis / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D016207:Cytokines; C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors
Immunity. 1999 Dec;11(6):677-88
10626890
Immunity. 1998 Oct;9(4):555-63
9806641
Cell. 2000 Mar 17;100(6):655-69
10761931
Oncogene. 2000 Apr 20;19(17):2086-97
10815800
J Immunol. 2000 Jul 1;165(1):286-91
10861063
J Immunol. 2000 Jul 1;165(1):292-6
10861064
Genes Dev. 2000 Jul 15;14(14):1693-711
10898785
J Exp Med. 2000 Jul 17;192(2):295-302
10899916
J Exp Med. 2000 Aug 7;192(3):325-36
10934221
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 2):S185-9
11029392
Annu Rev Immunol. 2001;19:683-765
11244051
Immunity. 2001 Mar;14(3):205-15
11290331
Science. 2001 Jun 8;292(5523):1907-10
11397944
J Immunol. 2001 Oct 15;167(8):4414-20
11591766
Nat Rev Mol Cell Biol. 2001 Nov;2(11):827-37
11715049
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15137-42
11752460
Nat Immunol. 2002 Jun;3(6):549-57
12006974
Nat Immunol. 2002 Jul;3(7):652-8
12055627
J Clin Invest. 2002 Sep;110(6):843-50
12235116
J Immunol. 2002 Oct 15;169(8):4205-12
12370350
Gene. 2003 Jan 16;303:11-34
12559563
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13887-92
9811896
Immunity. 1998 Nov;9(5):745-55
9846495
J Biol Chem. 1999 Apr 30;274(18):12910-6
10212281
J Exp Med. 1999 Oct 4;190(7):995-1004
10510089
Annu Rev Immunol. 2003;21:713-58
12500979
Immunity. 2003 May;18(5):605-17
12753738
Int Immunol. 2003 Oct;15(10):1149-60
13679385
Immunity. 2003 Nov;19(5):739-48
14614860
J Immunol. 2004 Jan 1;172(1):114-22
14688316
Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1993-8
14769923
J Immunol. 2004 Mar 15;172(6):3704-11
15004174
Immunity. 2004 Apr;20(4):477-94
15084276
J Immunol. 1989 Jan 15;142(2):672-8
2536061
Annu Rev Immunol. 1989;7:145-73
2523712
Proc Natl Acad Sci U S A. 1990 May;87(10):3723-7
2187191
Science. 1990 Dec 21;250(4988):1720-3
2125367
J Immunol. 1993 Jun 1;150(11):4754-65
7684412
J Immunol. 1995 Mar 15;154(6):2724-32
7876544
Immunity. 1994 Oct;1(7):553-62
7600284
Nature. 1995 Oct 19;377(6550):635-8
7566176
Nature. 1995 Oct 19;377(6550):639-42
7566177
J Interferon Cytokine Res. 1997 Jan;17(1):1-10
9041465
J Exp Med. 1997 Mar 3;185(5):817-24
9120387
J Virol. 1997 May;71(5):3563-73
9094628
Cell. 1997 May 16;89(4):587-96
9160750
J Exp Med. 1997 Jun 16;185(12):2101-10
9182682
Oncogene. 1997 Jun 12;14(23):2845-55
9190901
Nature. 1997 Oct 16;389(6652):737-42
9338786
Int Rev Immunol. 1998;16(3-4):427-55
9505198
J Immunol. 2000 Mar 15;164(6):2857-60
10706669