The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway.
Interleukin 12 (IL-12)-induced T helper 1 (Th1) development requires Stat4 activation. However, antigen-activated Th1 cells can produce interferon gamma (IFN-gamma) independently of IL-12 and Stat4 activation. Thus, in differentiated Th1 cells, factors regulated by IL-12 and Stat4 may be involved in IFN-gamma production. Using subtractive cloning, we identified ERM, an Ets transcription factor, to be a Th1-specific, IL-12-induced gene. IL-12-induction of ERM occurred in wild-type and Stat1-deficient, but not Stat4-deficient, T cells, suggesting ERM is Stat4-inducible. Retroviral expression of ERM did not restore IFN-gamma production in Stat4-deficient T cells, but augmented IFN-gamma expression in Stat4-heterozygous T cells. Ets factors frequently regulate transcription via cooperative interactions with other transcription factors, and ERM has been reported to cooperate with c-Jun. However, in the absence of other transcription factors, ERM augmented expression of an IFN-gamma reporter by only 2-fold. Thus, determining the requirement for ERM in Th1 development likely will require gene targeting.
Ouyang
W
W
Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jacobson
N G
NG
Bhattacharya
D
D
Gorham
J D
JD
Fenoglio
D
D
Sha
W C
WC
Murphy
T L
TL
Murphy
K M
KM
D000818:Animals; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050797:STAT4 Transcription Factor; C494080:Stat1 protein, mouse; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12; D007371:Interferon-gamma