Activating transcription factor 3 is a negative regulator of allergic pulmonary inflammation.
We recently demonstrated the pivotal role of the transcription factor (TF) activating TF 3 (ATF3) in dampening inflammation. We demonstrate that ATF3 also ameliorates allergen-induced airway inflammation and hyperresponsiveness in a mouse model of human asthma. ATF3 expression was increased in the lungs of mice challenged with ovalbumin allergen, and this was associated with its recruitment to the promoters of genes encoding Th2-associated cytokines. ATF3-deficient mice developed significantly increased airway hyperresponsiveness, pulmonary eosinophilia, and enhanced chemokine and Th2 cytokine responses in lung tissue and in lung-derived CD4(+) lymphocytes. Although several TFs have been associated with enhanced inflammatory responses in the lung, ATF3 attenuates the inflammatory responses associated with allergic airway disease.
Gilchrist
Mark
M
Institute for Systems Biology, Seattle, WA 98103, USA.
Henderson
William R
WR
Clark
April E
AE
Simmons
Randi M
RM
Ye
Xin
X
Smith
Kelly D
KD
Aderem
Alan
A
D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000276:immunology*; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011657:Pulmonary Eosinophilia / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D051700:Activating Transcription Factor 3; D000485:Allergens; D018925:Chemokines; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4; D010047:Ovalbumin
Nature. 2006 May 11;441(7090):173-8
16688168
J Immunol. 2004 Dec 15;173(12):7565-74
15585884
J Allergy Clin Immunol. 2000 Feb;105(2 Pt 2):S547-58
10669540
Gene. 2001 Jul 25;273(1):1-11
11483355
N Engl J Med. 2001 Jan 4;344(1):30-7
11136958
J Immunol. 2008 Apr 1;180(7):4939-47
18354219
Nat Rev Immunol. 2003 May;3(5):405-12
12766762
N Engl J Med. 2001 Feb 1;344(5):350-62
11172168
Am J Respir Crit Care Med. 2001 Oct 15;164(8 Pt 1):1343-6
11704578
J Exp Med. 1998 Nov 2;188(9):1739-50
9802985
Eur J Immunol. 2000 Apr;30(4):1102-12
10760799
J Allergy Clin Immunol. 2002 Feb;109(2):238-45
11842291
J Interferon Cytokine Res. 2003 Jan;23(1):37-45
12639297
N Engl J Med. 2006 Nov 23;355(21):2226-35
17124020
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5545-50
11960012
Nat Rev Mol Cell Biol. 2001 Aug;2(8):599-609
11483993
J Immunol. 2003 Nov 15;171(10):5547-53
14607962
Nat Immunol. 2003 Jul;4(7):616-23
12830136
J Exp Med. 2007 Apr 16;204(4):865-77
17403936
Am J Respir Cell Mol Biol. 2006 Sep;35(3):337-46
16645178
J Biol Chem. 1995 Jul 21;270(29):17541-50
7615560
Oncogene. 2006 Oct 30;25(51):6831-43
17072331
EMBO J. 2002 Dec 2;21(23):6321-9
12456639
Annu Rev Immunol. 2006;24:607-56
16551261
Chest. 2000 May;117(5):1482-7
10807839
J Immunol. 2002 Mar 15;168(6):2953-62
11884467
EMBO J. 1999 Jan 15;18(2):420-32
9889198
Biochem Soc Trans. 2003 Feb;31(Pt 1):60-5
12546654
Int Immunol. 1997 Sep;9(9):1329-38
9310836
Lab Invest. 2006 Sep;86(9):867-72
16865089
J Biol Chem. 2002 May 24;277(21):18313-21
11893731
Nat Immunol. 2002 Jul;3(7):643-51
12055628
Immunity. 2002 Jul;17(1):7-17
12150887
Mol Immunol. 2007 Mar;44(7):1598-605
16982098
J Exp Med. 1998 Jul 6;188(1):157-67
9653092
J Clin Invest. 2006 Feb;116(2):309-21
16453019
Nat Rev Immunol. 2003 Jul;3(7):534-43
12876556
J Clin Invest. 1999 Oct;104(8):995-9
10525033
Cell Growth Differ. 1995 May;6(5):531-40
7647036
Immunity. 2000 Jan;12(1):27-37
10661403