The Ets transcription factor ERM is Th1-specific and induced by 1 IL-12 through a Stat4-dependent pathway

摘要

Interleukin 12 (IL-12)-induced T helper 1 (Thl) development requires Stat4 activation. However, anti- gen-activated Thl. cells can produce interferon gamma (IFN-Y) independently of IL.12 and Stat4 activation. Thus, in differ- entiatcd Thl 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 Thl. specific, IL-12-induced gene. IL-12-inductiOn of ERM oc- curred in wild-type and Stat1-deficient, but not Stat4- deficient, T cells, suggesting ERM is Stat4-inducible. Retro- viral 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 tran- scription factors, and ERN 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.