The 3' Enhancer CNS2 Is a Critical Regulator of Interleukin-4-Mediated Humoral Immunity in Follicular Helper T Cells

Yohsuke Harada, Shinya Tanaka, Yasutaka Motomura, Yasuyo Harada, Shin Ichiro Ohno, Shinji Ohno, Yusuke Yanagi, Hiromasa Inoue, Masato Kubo

Research output: Contribution to journalArticle

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Abstract

A main role for interleukin-4 (IL-4) is in humoral immunity, and follicular helper CD4 + T (Tfh) cells may be an intrinsic IL-4 source. Here we demonstrate that conserved noncoding sequence 2 (CNS2) is an essential enhancer element for IL-4 expression in Tfh cells but not in Th2 cells. Mice with a CNS2 deletion had a reduction in IgG1 and IgE production and in IL-4 expression in Tfh cells. Tracking of CNS2 activity via a GFP reporter mouse demonstrated that CNS2-active cells expressed several markers of Tfh cells: CXCR5, PD-1, and ICOS; the transcriptional master regulator Bcl6; and the cytokines IL-21 and IL-4. These CNS2-active cells were mainly localized in B cell follicles and germinal centers. The GFP + Tfh cells were derived from GFP - naive T cells after in vivo systemic immunization. These results indicate that CNS2 is an essential enhancer element required for IL-4 expression in Tfh cells controlling humoral immunity.

Original languageEnglish
Pages (from-to)188-200
Number of pages13
JournalImmunity
Volume36
Issue number2
DOIs
Publication statusPublished - Feb 24 2012

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Conserved Sequence
Humoral Immunity
Helper-Inducer T-Lymphocytes
Interleukin-4
Th2 Cells
Germinal Center
Sequence Deletion
Immunoglobulin E
Immunization
B-Lymphocytes
Immunoglobulin G
Cytokines
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Harada, Y., Tanaka, S., Motomura, Y., Harada, Y., Ohno, S. I., Ohno, S., ... Kubo, M. (2012). The 3' Enhancer CNS2 Is a Critical Regulator of Interleukin-4-Mediated Humoral Immunity in Follicular Helper T Cells. Immunity, 36(2), 188-200. https://doi.org/10.1016/j.immuni.2012.02.002

The 3' Enhancer CNS2 Is a Critical Regulator of Interleukin-4-Mediated Humoral Immunity in Follicular Helper T Cells. / Harada, Yohsuke; Tanaka, Shinya; Motomura, Yasutaka; Harada, Yasuyo; Ohno, Shin Ichiro; Ohno, Shinji; Yanagi, Yusuke; Inoue, Hiromasa; Kubo, Masato.

In: Immunity, Vol. 36, No. 2, 24.02.2012, p. 188-200.

Research output: Contribution to journalArticle

Harada, Y, Tanaka, S, Motomura, Y, Harada, Y, Ohno, SI, Ohno, S, Yanagi, Y, Inoue, H & Kubo, M 2012, 'The 3' Enhancer CNS2 Is a Critical Regulator of Interleukin-4-Mediated Humoral Immunity in Follicular Helper T Cells', Immunity, vol. 36, no. 2, pp. 188-200. https://doi.org/10.1016/j.immuni.2012.02.002
Harada, Yohsuke ; Tanaka, Shinya ; Motomura, Yasutaka ; Harada, Yasuyo ; Ohno, Shin Ichiro ; Ohno, Shinji ; Yanagi, Yusuke ; Inoue, Hiromasa ; Kubo, Masato. / The 3' Enhancer CNS2 Is a Critical Regulator of Interleukin-4-Mediated Humoral Immunity in Follicular Helper T Cells. In: Immunity. 2012 ; Vol. 36, No. 2. pp. 188-200.
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