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

Nature Immunology volume 14, pages 90–99 (2013)Cite this article

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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.

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Figure 1: Upregulation of the expression of NKRs by iNKT cells at the end of thymic differentiation.
Figure 2: Expression of NKRs in peripheral CD4+ and CD4− iNKT cells.
Figure 3: The global transcriptional relationship between NK and iNKT cells is similar in magnitude to the relationship between T cells and iNKT cells.
Figure 4: Characterization of shared and different gene expression in iNKT cells, NK cells and T cells.
Figure 5: Transcriptional programs shared by NK cells and iNKT cells are acquired during thymic maturation of iNKT cells.
Figure 6: Activated splenic γδ T cells and IEL γδ T cells express genes in the program shared by NK cells and iNKT cells.
Figure 7: Programs shared by NK cells and iNKT cells are induced in activated CD8+ T cells.

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Acknowledgements

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).

Author information

Author notes

  1. Nadia R Cohen, Patrick J Brennan, Francis Kim, Tata Nageswara Rao and Amy Wagers: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Nadia R Cohen, Patrick J Brennan, Gerald F Watts, Manfred Brigl & Michael B Brenner

  2. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

    Tal Shay

  3. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Manfred Brigl

  4. Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Joonsoo Kang, Kavitha Narayan, Katelyn Sylvia & Joonsoo Kang

  5. Department of Medicine, Boston University, Boston, Massachusetts, USA

    Paul Monach

  6. Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA

    Susan A Shinton & Richard R Hardy

  7. Computer Science Department, Brown University, Providence, Rhode Island, USA

    Radu Jianu & David Koller

  8. Department of Biomedical Engineering, Howard Hughes Medical Institute, Boston University, Boston, Massachusetts, USA

    Jim Collins

  9. Immune Diseases Institute, Children's Hospital, Boston, Massachusetts, USA

    Roi Gazit, Brian S Garrison & Derrick J Rossi

  10. Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA

    Anne Fletcher, Kutlu Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon Turley & Taras Kreslavsky

  11. Division of Biological Sciences, University of California San Diego, La Jolla, California, USA

    Adam J Best, Jamie Knell & Ananda Goldrath

  12. Computer Science Department, Stanford University, Stanford, California, USA

    Vladimir Jojic & Daphne Koller

  13. Broad Institute, Cambridge, Massachusetts, USA

    Tal Shay & Aviv Regev

  14. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Nadia Cohen, Patrick Brennan & Michael Brenner

  15. Department of Microbiology & Immunology, University of California San Francisco, San Francisco, California, USA

    Natalie A Bezman, Joseph C Sun, Charlie C Kim & Lewis L Lanier

  16. Icahn Medical Institute, Mount Sinai Hospital, New York, New York, USA

    Jennifer Miller, Brian Brown, Miriam Merad, Emmanuel L Gautier, Claudia Jakubzick & Gwendalyn J Randolph

  17. Department of Pathology & Immunology, Washington University, St. Louis, Missouri, USA

    Emmanuel L Gautier & Gwendalyn J Randolph

  18. Joslin Diabetes Center, Boston, Massachusetts, USA

    Francis Kim, Tata Nageswara Rao & Amy Wagers

  19. Division of Immunology, Department of Microbiology & Immunobiology, Harvard Medical School, Boston, Massachusetts, USA

    Tracy Heng, Michio Painter, Jeffrey Ericson, Scott Davis, Ayla Ergun, Michael Mingueneau, Diane Mathis & Christophe Benoist

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  1. Nadia R Cohen
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Consortia

ImmGen Project Consortium

  • 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
  • , Joonsoo Kang
  • , Anne Fletcher
  • , Kutlu Elpek
  • , Angelique Bellemare-Pelletier
  • , Deepali Malhotra
  • , Shannon Turley
  • , Adam J Best
  • , Jamie Knell
  • , Ananda Goldrath
  • , Vladimir Jojic
  • , Daphne Koller
  • , Tal Shay
  • , Aviv Regev
  • , Nadia Cohen
  • , Patrick Brennan
  • , Michael Brenner
  • , 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

Contributions

N.R.C. primarily wrote the manuscript, conceived of and did experiments and analyzed the data; P.J.B. contributed substantially to the manuscript, conceived of and did experiments and analyzed the data; T.S. conceived of and did experiments and analyzed the data; G.F.W. did experiments; M.B. and J.K. assisted with experimental design and interpretation of the data; M.B.B. substantially contributed to the manuscript and supervised all experimental design, performance and data analysis; and The ImmGen Project Consortium contributed to experimental design and data collection.

Corresponding author

Correspondence to Michael B Brenner.

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The authors declare no competing financial interests.

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Cohen, N., Brennan, P., Shay, T. et al. Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells. Nat Immunol 14, 90–99 (2013). https://doi.org/10.1038/ni.2490

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