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

Lucille C. Rankin; Joanna R. Groom; Michaël Chopin; Marco J. Herold; Jennifer A. Walker; Lisa A. Mielke; Andrew N.J. McKenzie; Sebastian Carotta; Stephen L. Nutt; Gabrielle T. Belz

doi:10.1038/ni.2545

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

Lucille C. Rankin, Joanna R. Groom, Michaël Chopin, Marco J. Herold, Jennifer A. Walker, Lisa A. Mielke, Andrew N.J. McKenzie, Sebastian Carotta, Stephen L. Nutt, Gabrielle T. Belz

Research output: Contribution to journal › Article › Research › peer-review

247 Citations (Scopus)

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.

Original language	English
Pages (from-to)	389-395
Number of pages	7
Journal	Nature Immunology
Volume	14
Issue number	4
DOIs	https://doi.org/10.1038/ni.2545
Publication status	Published - Apr 2013
Externally published	Yes

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10.1038/ni.2545

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@article{4688ac92cf284077a72dea41796e6621,

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

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 reporTHere 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.",

author = "Rankin, {Lucille C.} and Groom, {Joanna R.} and Micha{\"e}l Chopin and Herold, {Marco J.} and Walker, {Jennifer A.} and Mielke, {Lisa A.} and McKenzie, {Andrew N.J.} and Sebastian Carotta and Nutt, {Stephen L.} and Belz, {Gabrielle T.}",

note = "Funding Information: 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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doi = "10.1038/ni.2545",

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AU - Rankin, Lucille C.

AU - Groom, Joanna R.

AU - Chopin, Michaël

AU - Herold, Marco J.

AU - Walker, Jennifer A.

AU - Mielke, Lisa A.

AU - McKenzie, Andrew N.J.

AU - Carotta, Sebastian

AU - Nutt, Stephen L.

AU - Belz, Gabrielle T.

N1 - Funding Information: 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.

PY - 2013/4

Y1 - 2013/4

N2 - 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 reporTHere 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.

AB - 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 reporTHere 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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DO - 10.1038/ni.2545

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VL - 14

SP - 389

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JO - Nature Immunology

JF - Nature Immunology

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ER -

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

Abstract

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Erratum: The transcription factor T-bet is essential for the development of NKp46 + innate lymphocytes via the Notch pathway (Nature Immunology (2013) 14 (389-395))

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