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Nat Immunol. 2013 Apr;14(4):389-95. doi: 10.1038/ni.2545. Epub 2013 Mar 3.

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

Author information

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

Erratum in

  • Nat Immunol. 2013 Aug;14(8):877.
  • Nat Immunol. 2013 Apr;14(4):395.

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.

PMID:
23455676
PMCID:
PMC4076532
DOI:
10.1038/ni.2545
[Indexed for MEDLINE]
Free PMC Article

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