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 language | English |
|---|---|
| Pages (from-to) | 689-701 |
| Number of pages | 13 |
| Journal | Immunity |
| Volume | 24 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2006 |
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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 journal › Article
}
TY - JOUR
T1 - The Interleukin-4 Enhancer CNS-2 Is Regulated by Notch Signals and Controls Initial Expression in NKT Cells and Memory-Type CD4 T Cells
AU - Tanaka, Shinya
AU - Tsukada, Jun
AU - Suzuki, Wataru
AU - Hayashi, Katsuhiko
AU - Tanigaki, Kenji
AU - Tsuji, Masayuki
AU - Inoue, Hiromasa
AU - Honjo, Tasuku
AU - Kubo, Masato
PY - 2006/6/1
Y1 - 2006/6/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33745081482&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2006.04.009
DO - 10.1016/j.immuni.2006.04.009
M3 - Article
C2 - 16782026
AN - SCOPUS:33745081482
VL - 24
SP - 689
EP - 701
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 6
ER -