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Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells

Cellular & Molecular Immunology volume 11, pages 232–244 (2014)Cite this article

Abstract

The interplay between the CD4-lineage transcription factor ThPok and the CD8-lineage transcription factor, runt-related transcription factor 3 (Runx3), in T-cell development has been extensively documented. However, little is known about the roles of these transcription factors in invariant natural killer T (iNKT) cell development. CD1d-restricted iNKT cells are committed to the CD4+CD8− and CD4−CD8− sublineages, which respond to antigen stimulation with rapid and potent release of T helper (Th) 1 and Th2 cytokines. However, previous reports have demonstrated a new population of CD8+ NKT cells in ThPok-deficient mice. In the current study, we sought to determine whether Runx3 was involved in the re-expression of CD8 and function of iNKT cells in the absence of ThPok. We used mice lacking Runx3, ThPok or both and verified that Runx3 was partially responsible for the appearance of CD8+ iNKT cells in ThPok knockout mice. Additionally, Runx3 participated in the immune response mediated by iNKT cells in a model of α-galactosylceramide-induced acute hepatitis. These results indicate that Runx3 is crucial for the phenotypic and functional changes observed in ThPok-deficient iNKT cells.

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Acknowledgements

We thank Dr. Rémy Bosselut for providing the CD4-cre+ThPokF/Fmice, Dr.Iain Bruce for editing the manuscript, and Yingying Huang for assistance with flow cytometry. This work was supported by grants from the National Natural Science Foundation of China (J20111945, J20121461 and C080102), the National Basic Research Program of China (973 Program and 863 Program) (2012CB966603, 2012ZX10002006 and 2012AA020901), the Zhejiang Provincial Natural Science Foundation of China (R20110298), the Doctoral Fund of the Ministry of Education of China (20110101120102) and the Fundamental Research Funds for the Central Universities

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  1. Dr L Wang, Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China. E-mail: wanglie@zju.edu.cn

  2. Dr JL Wang, Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China. E-mail: jlwang@zju.edu.cn

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  1. Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China

    Xia Liu, Shengxia Yin, Wenqiang Cao, Wei Fan, Lei Yu, Li Yin, Lie Wang & Jianli Wang

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Liu, X., Yin, S., Cao, W. et al. Runt-related transcription factor 3 is involved in the altered phenotype and function in ThPok-deficient invariant natural killer T cells. Cell Mol Immunol 11, 232–244 (2014). https://doi.org/10.1038/cmi.2014.3

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