Abstract
The transcriptional repressor Blimp-1 mediates the terminal differentiation of many cell types, including T cells. Here we identified Hobit (Znf683) as a previously unrecognized homolog of Blimp-1 that was specifically expressed in mouse natural killer T cells (NKT cells). Through studies of Hobit-deficient mice, we found that Hobit was essential for the formation of mature thymic NKT cells. In the periphery, Hobit repressed the accumulation of interferon-γ (IFN-γ)-producing NK1.1lo NKT cells at steady state. After antigenic stimulation, Hobit repressed IFN-γ expression, whereas after innate stimulation, Hobit induced granzyme B expression. Thus, reminiscent of the function of Blimp-1 in other lymphocytes, Hobit controlled the maintenance of quiescent, fully differentiated NKT cells and regulated their immediate effector functions.
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Acknowledgements
We thank L. Boon (Bioceros) for antibodies; J.C. Zúñiga-Pflücker (Sunnybrook Research Institute) for OP9-DL1 cells; the staff of the animal facility of the Academic Medical Center for animal care; A. de Bruin for technical assistance; B. Hooibrink, E. Mul and F. van Alphen for cell sorting; D. Edo-Matas for help with phylogenetic analysis; and A. Kallies for critical reading of the manuscript. Supported by The Netherlands Organization of Scientific Research (M.A.N. and R.A.W.v.L.) and the Landsteiner Foundation for Blood Transfusion Research (N.A.M.K.).
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K.P.J.M.v.G., N.A.M.K., K.M.L.H. and F.M.W. did experiments; K.P.J.M.v.G., S.J., J.H., M.A.N. and R.A.W.v.L. designed experiments; and K.P.J.M.v.G., M.A.N. and R.A.W.v.L. wrote the manuscript.
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van Gisbergen, K., Kragten, N., Hertoghs, K. et al. Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that regulates NKT cell effector differentiation. Nat Immunol 13, 864–871 (2012). https://doi.org/10.1038/ni.2393
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DOI: https://doi.org/10.1038/ni.2393
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