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

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Abstract
Invariant natural killer cells recognize glycolipids presented by CD1d molecules and can mediate rapid innate responses. Sant'Angelo and colleagues show that these cells express the transcription factor PLZF, which is required for their innate effector function. 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.