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The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway

Nature Immunology volume 14, pages 389395 (2013) | Download Citation

  • A Corrigendum to this article was published on 19 July 2013

This article has been updated


NKp46+ innate lymphoid cells (ILCs) serve important roles in regulating the intestinal microbiota and defense against pathogens. Whether NKp46+ ILCs arise directly from lymphoid tissue–inducer (LTi) cells or represent a separate lineage remains controversial. We report here that the transcription factor T-bet (encoded by Tbx21) was essential for the development of NKp46+ ILCs but not of LTi cells or nuocytes. Deficiency in interleukin 22 (IL-22)-producing NKp46+ ILCs resulted in greater susceptibility of Tbx21−/− mice to intestinal infection. Haploinsufficient T-bet expression resulted in lower expression of the signaling molecule Notch, and Notch signaling was necessary for the transition of LTi cells into NKp46+ ILCs. Furthermore, NKp46+ ILCs differentiated solely from the CD4 LTi population, not the CD4+ LTi population. Our results pinpoint the regulation of Notch signaling by T-bet as a distinct molecular pathway that guides the development of NKp46+ ILCs.

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Change history

  • 21 March 2013

    In the version of this article initially published, the key to Figure 1c was labeled incorrectly. The correct labeling is as follows: dotted line, Isotype; shaded box, T-bet. The error has been corrected in the HTML and PDF versions of the article.


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We thank R. Robins-Browne, M. Camilleri, R. Cole, J. Cruickshank and the staff of the animal and flow cytometry facilities of the Walter and Eliza Hall Institute and Medical Research Council Laboratory of Molecular Biology for technical assistance. Supported by the National Health and Medical Research Council of Australia (G.T.B., S.L.N., S.C., L.R. and J.R.G.), the Sylvia and Charles Viertel Foundation (G.T.B.), the Howard Hughes Medical Institute (G.T.B.), the Australian Research Council (S.L.N.), the Leukaemia Foundation (M.J.H.), the American Asthma Foundation (J.A.W.), the Medical Research Council, the American Asthma Foundation (A.N.J.M.) and Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council Independent Research Institutes Infrastructure Support Scheme.

Author information


  1. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

    • Lucille C Rankin
    • , Joanna R Groom
    • , Michaël Chopin
    • , Marco J Herold
    • , Lisa A Mielke
    • , Sebastian Carotta
    • , Stephen L Nutt
    •  & Gabrielle T Belz
  2. Department of Medical Biology, University of Melbourne, Melbourne, Australia.

    • Lucille C Rankin
    • , Joanna R Groom
    • , Michaël Chopin
    • , Marco J Herold
    • , Lisa A Mielke
    • , Sebastian Carotta
    • , Stephen L Nutt
    •  & Gabrielle T Belz
  3. Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.

    • Jennifer A Walker
    •  & Andrew N J McKenzie


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L.C.R., J.R.G., S.C., M.J.H., M.C., S.L.N. and G.T.B. designed and did experiments and analyzed data; L.A.M. did PCR analysis; J.A.W. and A.N.J.M. analyzed nuocytes; and G.T.B., L.C.R., J.R.G. and S.L.N. wrote the paper.

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Gabrielle T Belz.

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