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The BTB–zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions

Abstract

Invariant natural killer T cells (iNKT cells) have an innate immunity–like rapidity of response and the ability to modulate the effector functions of other cells. We show here that iNKT cells specifically expressed the BTB–zinc finger transcriptional regulator PLZF. In the absence of PLZF, iNKT cells developed, but they lacked many features of innate T cells. PLZF-deficient iNKT cells accumulated in lymph nodes rather than in the liver, did not express NK markers and did not have the characteristic activated phenotype. PLZF-deficient iNKT cells failed to secrete large amounts of interleukin 4 and interferon-γ after activation; however, some cells produced either interleukin 4 or interferon-γ but not both. PLZF, therefore, is an iNKT cell–specific transcription factor that is necessary for full functionality.

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Figure 1: High expression of PLZF in iNKT cells.
Figure 2: PLZF expression is limited to iNKT cells and does not affect the bulk of lymphocyte development.
Figure 3: Altered iNKT cell development in PLZF-deficient mice.
Figure 4: Altered liver iNKT cells in PLZF-deficient mice.
Figure 5: PLZF-deficient iNKTs accumulate in the lymph nodes and spleen.
Figure 6: PLZF-deficient iNKT cells do not rapidly produce cytokines.
Figure 7: PLZF-deficient iNKT present an altered cytokine secretion pattern.
Figure 8: Loss of PLZF expression affects the expression of many cytokines.

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Acknowledgements

We thank T. Martillotti for technical assistance; L. Denzin, J. Chaudhuri, E. Pamer and C.-H. Chang for critical reading of the manuscript and advice; and the Monoclonal Antibody and Flow Cytometry Core Facilities of Memorial Sloan-Kettering Cancer Center. Supported by the US National Institutes of Health (AI059739; T32 CA009149 to D.K.), the May and Samuel Rudin Family Foundation, the Memorial Sloan-Kettering Cancer Center and the US National Cancer Institute (P30-CA 08748 for the Monoclonal Antibody, Flow Cytometry, Research Animal Resource and Glassware Washing Core Facilities).

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D.K., O.U.U., S.E. and D.B.S. did most of the experiments; W.Y., E.A., K.C. and M.E. contributed to experiments; R.M.H., J.S.I. and P.P.P. contributed reagents and intellectual input; H.-J.K. contributed to the early stages of the study; D.K. and D.B.S. prepared the manuscript; and D.B.S. supervised the work.

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Correspondence to Derek B Sant'Angelo.

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Kovalovsky, D., Uche, O., Eladad, S. et al. The BTB–zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions. Nat Immunol 9, 1055–1064 (2008). https://doi.org/10.1038/ni.1641

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