Abstract
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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Acknowledgements
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.
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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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Rankin, L., Groom, J., Chopin, M. et al. The transcription factor T-bet is essential for the development of NKp46+ innate lymphocytes via the Notch pathway. Nat Immunol 14, 389–395 (2013). https://doi.org/10.1038/ni.2545
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DOI: https://doi.org/10.1038/ni.2545
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