Murine CD4+CD25+ regulatory T cells fail to undergo chromatin remodeling across the proximal promoter region of the IL-2 gene

Leon Su, Remi J. Creusot, Elena M. Gallo, Steven M. Chan, Paul J. Utz, C. Garrison Fathman, Joerg Ermann

Research output: Contribution to journalArticle

Abstract

CD4+CD25+ regulatory T cells (Treg) acquire unique immunosuppressive properties while maintaining an anergy phenotype when activated in vitro under conditions that induce IL-2 production and proliferation in conventional CD4+ T cells. We investigated the mechanism underlying one component of this naturally anergic phenotype, the inability of the Treg eels to produce IL-2 following activation. Analysis of freshly isolated murine CD4+CD25+ T reg and conventional CB4+CD25+ T cells following PMA/ ionomycin stimulation demonstrated no differences in indacible AP-1 formation, an important transcriptional complex in regulating IL-2 gene expression. Although p38 MAPK and ERK1/2 protein kinases were phosphorylated with similar kinetics, we observed diminished activation of JNK in the CD4 +CD25+ Treg cells. However, lentiviral-mediated reconstitution of the JNK pathway using a constitetively active construct did not overcome the block in IL-2 synthesis. Using a PCR-based chromatin accessibility assay we found that the minimal IL-2 promoter region of CD4 +CD25+ Treg cells, unlike conventional CD4 T cells, did not undergo chromatin remodeling following stimulation, suggesting that the inability of CD4+CD25+ Treg cells to secrete IL-2 following activation is controlled at the chromatin level.

Original languageEnglish (US)
Pages (from-to)4994-5001
Number of pages8
JournalJournal of Immunology
Volume173
Issue number8
DOIs
StatePublished - Oct 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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