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 journalArticle

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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 1 2006

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Natural Killer T-Cells
Conserved Sequence
Interleukin-4
T-Lymphocytes
Phenotype
CD4 Antigens
Interleukin-13
Viral Tumor Antigens
Epigenomics
Immunoglobulin E
Chromatin
Fluorescence

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

The Interleukin-4 Enhancer CNS-2 Is Regulated by Notch Signals and Controls Initial Expression in NKT Cells and Memory-Type CD4 T Cells. / Tanaka, Shinya; Tsukada, Jun; Suzuki, Wataru; Hayashi, Katsuhiko; Tanigaki, Kenji; Tsuji, Masayuki; Inoue, Hiromasa; Honjo, Tasuku; Kubo, Masato.

In: Immunity, Vol. 24, No. 6, 01.06.2006, p. 689-701.

Research output: Contribution to journalArticle

Tanaka, Shinya ; Tsukada, Jun ; Suzuki, Wataru ; Hayashi, Katsuhiko ; Tanigaki, Kenji ; Tsuji, Masayuki ; Inoue, Hiromasa ; Honjo, Tasuku ; Kubo, Masato. / The Interleukin-4 Enhancer CNS-2 Is Regulated by Notch Signals and Controls Initial Expression in NKT Cells and Memory-Type CD4 T Cells. In: Immunity. 2006 ; Vol. 24, No. 6. pp. 689-701.
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