Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells

Nadia R. Cohen, Patrick J. Brennan, Tal Shay, Gerald F. Watts, Manfred Brigl, Joonsoo Kang, Michael B. Brenner, Paul Monach, Susan A. Shinton, Richard R. Hardy, Radu Jianu, David Koller, Jim Collins, Roi Gazit, Brian S. Garrison, Derrick J. Rossi, Kavitha Narayan, Katelyn Sylvia, Anne Fletcher, Kutlu ElpekAngelique Bellemare-Pelletier, Deepali Malhotra, Shannon Turley, Adam J. Best, Jamie Knell, Ananda Goldrath, Vladimir Jojic, Daphne Koller, Aviv Regev, Nadia Cohan, Patrick Brennen, Michael Brennar, Taras Kreslavsky, Natalie A. Bezman, Joseph C. Sun, Charlie C. Kim, Lewis L. Lanier, Jennifer Miller, Brian Brown, Miriam Merad, Emmanuel L. Gautier, Claudia Jakubzick, Gwendalyn J. Randolph, Francis Kim, Tata Nageswara Rao, Amy Wagers, Tracy Heng, Michio Painter, Jeffrey Ericson, Scott Davis, Ayla Ergun, Michael Mingueneau, Diane Mathis, Christophe Benoist

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Invariant natural killer T cells (iNKT cells) are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled gene expression in iNKT cells during ontogeny and in peripheral subsets as part of the Immunological Genome Project. High-resolution comparative transcriptional analyses defined developmental and subset-specific programs of gene expression by iNKT cells. In addition, we found that iNKT cells shared an extensive transcriptional program with NK cells, similar in magnitude to that shared with major histocompatibility complex (MHC)-restricted T cells. Notably, the program shared by NK cells and iNKT cells also operated constitutively in γδ T cells and in adaptive T cells after activation. Together our findings highlight a core effector program regulated distinctly in innate and adaptive lymphocytes.

Original languageEnglish (US)
Pages (from-to)90-99
Number of pages10
JournalNature immunology
Volume14
Issue number1
DOIs
StatePublished - Jan 2013

Bibliographical note

Funding Information:
We thank the tetramer facility of the US National Institutes of Health for ongoing support; and S. Raychaudhuri, X. Hu and H. Li for advice, discussions and technical assistance. Supported by the US National Institutes of Health (R01AI063428 to M.B.B., T32AI007306 to P.J.B, and R24AI072073 to the ImmGen Project consortium).

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