Article abstract
Nature Immunology 9, 1055 - 1064 (2008)
Published online: 27 July 2008 | doi:10.1038/ni.1641
The BTB–zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions
Damian Kovalovsky1,8, Olisambu U Uche2,8, Sonia Eladad1,8, Robin M Hobbs3,7, Woelsung Yi1, Eric Alonzo4, Kevin Chua1, Maggie Eidson5, Hye-Jung Kim1, Jin S Im6, Pier Paolo Pandolfi3,7 & Derek B Sant'Angelo1,2,4
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-
after activation; however, some cells produced either interleukin 4 or interferon- but not both. PLZF, therefore, is an iNKT cell–specific transcription factor that is necessary for full functionality.
- Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
- Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10065, USA.
- Cancer Biology and Genetics Program, Sloan-Kettering Institute, New York, New York 10065, USA.
- Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, New York, New York 10065, USA.
- Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
- Present address: Cancer Genetics Program and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
- These authors contributed equally to this work.
Correspondence to: Derek B Sant'Angelo1,2,4 e-mail: santangd@mskcc.org
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