Cutting edge: Ikaros is a regulator of Th2 cell differentiation

J Immunol. 2009 Jan 15;182(2):741-5. doi: 10.4049/jimmunol.182.2.741.

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 Ikaros(null) mice cultured under Th2-skewing conditions express the Th1 cytokine IFN-gamma 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 Ikaros(null)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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Chromatin / genetics
  • Chromatin / metabolism
  • Gene Expression Regulation / immunology
  • Hematopoiesis / genetics
  • Hematopoiesis / immunology
  • Ikaros Transcription Factor / deficiency
  • Ikaros Transcription Factor / genetics
  • Ikaros Transcription Factor / metabolism
  • Ikaros Transcription Factor / physiology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Immunological
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / cytology*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Transcriptional Activation / immunology
  • Up-Regulation / genetics
  • Up-Regulation / immunology*

Substances

  • Chromatin
  • Zfpn1a1 protein, mouse
  • Ikaros Transcription Factor
  • Interferon-gamma