W. Ouyang et al., The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway, P NAS US, 96(7), 1999, pp. 3888-3893
Citations number
45
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Interleukin 12 (IL-12)-induced T helper 1 (Th1) development requires Stat4
activation. However, antigen-activated Th1 cells can produce interferon gam
ma (IFN-gamma) independently of IL-12 and Stat4 activation. Thus, in differ
entiated 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-indu
ction of ERM occurred in wild-type and Stat1-deficient, but not Stat4-defic
ient, T cells, suggesting ERM is Stat4-inducible. Retroviral expression of
ERM did not restore IFN-gamma production in Stat4-deficient T cells, but au
gmented IFN-gamma expression in Stat4-heterozygous T cells. Ets factors fre
quently regulate transcription via cooperative interactions with other tran
scription factors, and ERM has been reported to cooperate with c-Jun, Howev
er, in the absence of other transcription factors, ERM augmented expression
of an IFN-y reporter by only 2-fold. Thus, determining the requirement for
ERM in Th1 development likely will require gene targeting.