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

Wenjun Ouyang, Nils G. Jacobson, Deepta Bhattacharya, James D. Gorham, Domenic Fenoglio, William C. Sha, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Interleukin 12 (IL-12)-induced T helper 1 (Th1) development requires Stat4 activation. However, antigen-activated Th1 cells can produce interferon γ (IFN-γ) independently of IL-12 and Stat4 activation. Thus, in differentiated Th1 cells, factors regulated by IL-12 and Stat4 may be involved in IFN-γ 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-γ production in Stat4-deficient T cells, but augmented IFN-γ 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-γ reporter by only 2-fold. Thus, determining the requirement for ERM in Th1 development likely will require gene targeting.

Original languageEnglish (US)
Pages (from-to)3888-3893
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number7
DOIs
StatePublished - Mar 30 1999
Externally publishedYes

ASJC Scopus subject areas

  • General

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