Abstract
The immunoregulatory cytokine interleukin 10 (IL-10) is expressed mainly by T helper type 2 (TH2) cells but also by TH1 cells during chronic infection. Here we observed plasticity in the expression of IL-10 and IL-13 after chronic TH1 stimulation; furthermore, the expression of Il10 and Il13 was regulated by the transcription factor E4BP4. Chronically stimulated E4BP4-deficient (Nfil3−/−; called 'E4bp4−/−' here) TH1 cells, regulatory T cells (Treg 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 TH1 cells. E4bp4−/− TH2 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 TH1 cells and IL-10 in TH1 cells, TH2 cells, Treg cells and NKT cells.
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Change history
09 August 2011
In the version of this article initially published, the text on page 455 describing the results for Figure 6d was inaccurate. The corrected text should read as follows: "...however, in response to stimulation with α-GalCer, E4bp4-/- NKT cells had no detectable IL-10 expression and lower IL-13 expression, and in response to IL-25, E4bp4-/- NKT cells had lower IL-13 expression and both wild-type and E4bp4-/- NKT cells had no detectable IL-10, whereas the expression of IFN-γ and IL-4 was unaffected (Fig. 6d)." In addition, the third column of Figure 6d should include the label 'ND' above all absent bars, and the legend should define 'ND' as 'not detected'. The errors have been corrected in the HTML and PDF versions of the article.
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Acknowledgements
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.
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Y. Motomura built the initial constructs, generated mouse lines and confirmed them in vivo, and did most of the experiments; H.K. and A.H. did microarray and bioinformatics analysis; Y. Matsunaga, K.M. and H.I. did airway hyper-responsiveness experiments; K.A. provided Il10 reporter mice; S.H. analyzed Treg cells; H.W. and M.T. analyzed NKT cells; J.Z. provided materials; and M.K. designed and coordinated experiments, supervised the project and wrote the paper.
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Supplementary Figures 1–10 and Supplementary Table 1 (PDF 1381 kb)
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Motomura, Y., Kitamura, H., Hijikata, A. et al. The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells. Nat Immunol 12, 450–459 (2011). https://doi.org/10.1038/ni.2020
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DOI: https://doi.org/10.1038/ni.2020
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