The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells

Yasutaka Motomura; Hiroshi Kitamura; Atsushi Hijikata; Yuko Matsunaga; Koichiro Matsumoto; Hiromasa Inoue; Koji Atarashi; Shohei Hori; Hiroshi Watarai; Jinfang Zhu; Masaru Taniguchi; Masato Kubo

doi:10.1038/ni.2020

The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4⁺ T cells

Yasutaka Motomura, Hiroshi Kitamura, Atsushi Hijikata, Yuko Matsunaga, Koichiro Matsumoto, Hiromasa Inoue, Koji Atarashi, Shohei Hori, Hiroshi Watarai, Jinfang Zhu, Masaru Taniguchi, Masato Kubo

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

158 Citations (Scopus)

Abstract

The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (T_H 2) cells but also by T_H 1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic T_H 1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3 ^-/-; called 'E4bp4 ^-/- ' here) T_H 1 cells, regulatory T cells (T reg cells) and natural killer T cells (NKT cells) had attenuated expression of IL-10 and IL-13. Enforced expression of E4bp4 initiated the production of IL-10 and IL-13 by conventional T_H 1 cells. E4bp4^-/- T_H 2 cells showed impairment of IL-10 production with no effect on IL-13. Our results indicate that E4BP4 has multiple functions in controlling the plasticity of IL-13 in T_H 1 cells and IL-10 in T_H 1 cells, T_H 2 cells, T_reg cells and NKT cells.

Original language	English
Pages (from-to)	450-459
Number of pages	10
Journal	Nature Immunology
Volume	12
Issue number	5
DOIs	https://doi.org/10.1038/ni.2020
Publication status	Published - 2011 May

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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@article{802e9a0ce0c347368892fb8c6b6cdd29,

title = "The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells",

abstract = "The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (TH 2) cells but also by TH 1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic TH 1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3 -/-; called 'E4bp4 -/- ' here) TH 1 cells, regulatory T cells (T reg cells) and natural killer T cells (NKT cells) had attenuated expression of IL-10 and IL-13. Enforced expression of E4bp4 initiated the production of IL-10 and IL-13 by conventional TH 1 cells. E4bp4-/- TH 2 cells showed impairment of IL-10 production with no effect on IL-13. Our results indicate that E4BP4 has multiple functions in controlling the plasticity of IL-13 in TH 1 cells and IL-10 in TH 1 cells, TH 2 cells, Treg cells and NKT cells.",

author = "Yasutaka Motomura and Hiroshi Kitamura and Atsushi Hijikata and Yuko Matsunaga and Koichiro Matsumoto and Hiromasa Inoue and Koji Atarashi and Shohei Hori and Hiroshi Watarai and Jinfang Zhu and Masaru Taniguchi and Masato Kubo",

note = "Funding Information: We thank K. Murphy (Washington University) for DO11.10 mice on the BALB/c background; S. Akira (Osaka University) for Stat6−/− mice; F. Brombacher (University of Cape Town) for Il4r−/− mice; C. Wilson (Washington University) for Cd4-Cre mice; R. Abe (Tokyo University of Science) for the PV-1 mAb to CD28; T. Kitamura (Tokyo University) for Platinum-E packaging cells; H. Fujimoto, Y. Suzuki, K. Ikari and E. Hayashi for technical assistance; and P. Burrows for comments on the manuscript. Supported by RIKEN (Y. Motomura), the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation.",

year = "2011",

month = may,

doi = "10.1038/ni.2020",

language = "English",

volume = "12",

pages = "450--459",

journal = "Nature Immunology",

issn = "1529-2908",

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T1 - The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells

AU - Motomura, Yasutaka

AU - Kitamura, Hiroshi

AU - Hijikata, Atsushi

AU - Matsunaga, Yuko

AU - Matsumoto, Koichiro

AU - Inoue, Hiromasa

AU - Atarashi, Koji

AU - Hori, Shohei

AU - Watarai, Hiroshi

AU - Zhu, Jinfang

AU - Taniguchi, Masaru

AU - Kubo, Masato

N1 - Funding Information: We thank K. Murphy (Washington University) for DO11.10 mice on the BALB/c background; S. Akira (Osaka University) for Stat6−/− mice; F. Brombacher (University of Cape Town) for Il4r−/− mice; C. Wilson (Washington University) for Cd4-Cre mice; R. Abe (Tokyo University of Science) for the PV-1 mAb to CD28; T. Kitamura (Tokyo University) for Platinum-E packaging cells; H. Fujimoto, Y. Suzuki, K. Ikari and E. Hayashi for technical assistance; and P. Burrows for comments on the manuscript. Supported by RIKEN (Y. Motomura), the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation.

PY - 2011/5

Y1 - 2011/5

N2 - The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (TH 2) cells but also by TH 1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic TH 1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3 -/-; called 'E4bp4 -/- ' here) TH 1 cells, regulatory T cells (T reg cells) and natural killer T cells (NKT cells) had attenuated expression of IL-10 and IL-13. Enforced expression of E4bp4 initiated the production of IL-10 and IL-13 by conventional TH 1 cells. E4bp4-/- TH 2 cells showed impairment of IL-10 production with no effect on IL-13. Our results indicate that E4BP4 has multiple functions in controlling the plasticity of IL-13 in TH 1 cells and IL-10 in TH 1 cells, TH 2 cells, Treg cells and NKT cells.

AB - The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (TH 2) cells but also by TH 1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic TH 1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3 -/-; called 'E4bp4 -/- ' here) TH 1 cells, regulatory T cells (T reg cells) and natural killer T cells (NKT cells) had attenuated expression of IL-10 and IL-13. Enforced expression of E4bp4 initiated the production of IL-10 and IL-13 by conventional TH 1 cells. E4bp4-/- TH 2 cells showed impairment of IL-10 production with no effect on IL-13. Our results indicate that E4BP4 has multiple functions in controlling the plasticity of IL-13 in TH 1 cells and IL-10 in TH 1 cells, TH 2 cells, Treg cells and NKT cells.

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DO - 10.1038/ni.2020

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JO - Nature Immunology

JF - Nature Immunology

IS - 5

ER -

The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4⁺ T cells

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