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The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell–mediated peripheral T cell unresponsiveness

Nature Immunology volume 11, pages 962–968 (2010)Cite this article

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Abstract

Induced regulatory T cells (iTreg cells) can be generated by peripheral dendritic cells (DCs) that mediate T cell unresponsiveness to rechallenge with antigen. The molecular factors required for the function of such iTreg cells remain unknown. We report a critical role for the transcription cofactor homeodomain-only protein (Hop; also known as Hopx) in iTreg cells to mediate T cell unresponsiveness in vivo. Hopx-sufficient iTreg cells downregulated expression of the transcription factor AP-1 complex and suppressed other T cells. In the absence of Hopx, iTreg cells had high expression of the AP-1 complex, proliferated and failed to mediate T cell unresponsiveness to rechallenge with antigen. Thus, Hopx is required for the function of Treg cells induced by DCs and the promotion of DC-mediated T cell unresponsiveness in vivo.

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Figure 1: Hopx expressed in iTreg cells is required for T cell unresponsiveness.
Figure 2: Hopx-deficient iTreg cells express Treg cell–specific genes but fail to mediate T cell unresponsiveness in vivo.
Figure 3: Hopx-dependent expression of proliferation-related genes in DC-induced Treg cells.
Figure 4: Hopx maintains the state of anergy in DC-induced Treg cells.

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Acknowledgements

We thank E. Olson (University of Texas Southwestern Medical Center) for Hopx−/− mice; T. Taylor for help with cell sorting; and L. Zenewicz and F. Manzo for help during preparation of the manuscript. Supported by the American Diabetes Society (D.H.), the National Multiple Sclerosis Society (TA 3024A1/2 to D.H.) and the Howard Hughes Medical Institute (R.A.F.).

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Authors and Affiliations

  1. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA

    Daniel Hawiger, Elizabeth E Eynon & Richard A Flavell

  2. Department of Microbiology and Immunology, UNC School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA

    Yisong Y Wan

  3. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA

    Elizabeth E Eynon & Richard A Flavell

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  1. Daniel Hawiger
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D.H. designed and did experiments, interpreted data and wrote the manuscript; Y.Y.W. produced FIR mice; E.E.E. contributed to interpretation of data; and R.A.F. oversaw the experimental design, interpreted data and wrote the manuscript.

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Correspondence to Richard A Flavell.

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Hawiger, D., Wan, Y., Eynon, E. et al. The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell–mediated peripheral T cell unresponsiveness. Nat Immunol 11, 962–968 (2010). https://doi.org/10.1038/ni.1929

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