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Transcription factor IRF8 controls Th1-like regulatory T-cell function

Cellular & Molecular Immunology volume 13, pages 785–794 (2016)Cite this article

Abstract

Recent studies have suggested that regulatory T (Treg) cells comprise a heterogeneous population that regulates various aspects of the immune response, and that Treg cells use the factors that are expressed in their target cells to regulate them. We searched for factors that regulate Th1 response in Treg cells using a meta-analysis. In the process, we discovered that transcription factor interferon regulatory factor 8 (IRF8) was selectively expressed in Treg and Th1 cells. IRF8-deficient Treg cells showed defective expression of CXCR3 and aberrant expression of the Il4 and Il17 genes. Upon treatment with alpha galactosyl-C18-ceramide (αGal-C18-Cer), IRF8-deficient mice showed defective Treg cell recruitment in the liver. Eliciting Th1 immune response by anti-CD40 antibody injection in mice induced IRF8 expression in Treg cells. The expression of IRF8 was induced by Foxp3 in Treg cells. IRF8 had no effect on T-bet expression in Treg and vice versa. Thus, our results strongly suggest that IRF8 controls Th1 immune response in Treg cells independent of T-bet.

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Acknowledgements

We thank Drs. Keiko Ozato (National Institutes of Health) and Tomohiko Tamura (Yokohama City University) for providing and transferring IRF8-deficient mice, respectively. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF-2010-0017447 and NRF-2014R1A2A1A11052545).

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  1. Gap Ryol Lee, Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742, Korea. E-mail: grlee@sogang.ac.kr

Authors and Affiliations

  1. Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 121-742, Korea

    Wonyong Lee, Hyeong Su Kim, Song Yi Baek & Gap Ryol Lee

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Lee, W., Kim, H., Baek, S. et al. Transcription factor IRF8 controls Th1-like regulatory T-cell function. Cell Mol Immunol 13, 785–794 (2016). https://doi.org/10.1038/cmi.2015.72

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