The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells

H. Daniel Lacorazza, Yasushi Miyazaki, Antonio Di Cristofano, Anthony Deblasio, Cyrus Hedvat, Jin Zhang, Carlos Cordon-Cardo, Shifeng Mao, Pier Paolo Pandolfi, Stephen D. Nimer

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

We utilized gene targeting by homologous recombination to define the role that MEF, a transcriptional activating member of the ETS family of transcription factors, plays in lymphopoiesis. MEF-/- mice have a profound reduction in the number of NK-T and NK cells. Purified MEF-/- NK cells cannot lyse tumor cell targets and secrete only minimal amounts of IFNγ. Perforin protein expression is severely impaired in MEF-deficient NK cells, likely accounting for the lack of tumor cell cytotoxicity. Promoter studies and chromatin immunoprecipitation analyses demonstrate that MEF and not ETS-1 directly regulates transcription of the perforin gene in NK cells. Our results uncover a specific role of MEF in the development and function of NK cells and in innate immunity.

Original languageEnglish (US)
Pages (from-to)437-449
Number of pages13
JournalImmunity
Volume17
Issue number4
DOIs
StatePublished - Oct 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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