The Interleukin-4 Enhancer CNS-2 Is Regulated by Notch Signals and Controls Initial Expression in NKT Cells and Memory-Type CD4 T Cells

Shinya Tanaka, Jun Tsukada, Wataru Suzuki, Katsuhiko Hayashi, Kenji Tanigaki, Masayuki Tsuji, Hiromasa Inoue, Tasuku Honjo, Masato Kubo

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)

Abstract

Epigenetic changes in chromatin structure at the T helper (Th2) locus correlate with interukin-4 (IL-4) and IL-13 expression during Th2 differentiation. By using a transgenic green fluorescence protein (GFP) reporter system, we show that conserved noncoding sequence-2 (CNS-2), located downstream of the Il4 locus, is a constitutively active enhancer in NKT cells as well as in a subset of CD44hi memory phenotype CD4+ T cells. CNS-2 enhancer activity and initial IL-4 expression in CD44hi CD4+ T cells were abolished in mice with a CD4-specific deletion of the transcriptional mediator of Notch signaling, Rbp-j. Depletion of CNS-2 active CD4+ T cells markedly decreased Th2 differentiation from naive CD4 T cells and antigen-specific IgE production after in vivo priming. These findings indicate that Notch-regulated CNS-2 enhancer controls initial IL-4 expression in NKT and memory phenotype CD4+ T cells and that CNS-2 active CD44hi memory phenotype T cells are important in facilitating Th2 differentiation of naive CD4+ T cells in allergic responses.

Original languageEnglish
Pages (from-to)689-701
Number of pages13
JournalImmunity
Volume24
Issue number6
DOIs
Publication statusPublished - Jun 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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