Cutting edge: Ikaros is a regulator of Th2 cell differentiation

Mary R. Quirion, Gregory D. Gregory, Sarah E. Umetsu, Susan Winandy, Melissa A. Brown

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Ikaros, a hematopoietic transcription factor, has well defined effects on early lymphocyte development in the bone marrow and thymus. In this study we demonstrate that Ikaros is a positive regulator of Th2 cytokine gene expression in peripheral T cells. CD4+ T cells from naive Ikarosnull mice cultured under Th2-skewing conditions express the Th1 cytokine IFN-γ and have reduced IL-4, IL-5, and IL-13 expression. Ikaros directly associates with several Th2 locus regulatory regions in naive CD4+ T cells. The decreased ability to express Th2 cytokines in Ikarosnull T cells corresponds with histone 3 hypoacetylation across the Th2 cytokine locus as well as decreased GATA3 and cMaf and increased T-bet and STAT1 expression. These data support a model whereby Ikaros directly activates Th2 gene expression by promoting local chromatin accessibility during CD4+ T cell differentiation and also acts indirectly to regulate expression of Th2- and Th1-specific transcription factors.

Original languageEnglish (US)
Pages (from-to)741-745
Number of pages5
JournalJournal of Immunology
Volume182
Issue number2
DOIs
StatePublished - Jan 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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