The transcription factor T-bet is essential for the development of NKp46(+) innate lymphocytes via the Notch pathway
Details
Publication Year 2013-04, Volume 14, Issue #4, Page 389-395
Journal Title
NATURE IMMUNOLOGY
Publication Type
Journal Article
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 1-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 1-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 1-bet as a distinct molecular pathway that guides the development of NKp46(+) ILCs.
Publisher
NATURE PUBLISHING GROUP
Keywords
ROR-GAMMA-T; TISSUE INDUCER CELLS; LYMPHOID-CELLS; EXPRESSION; IMMUNITY; FETAL; FATE; ID2; INFLAMMATION; CHECKPOINTS
WEHI Research Division(s)
Molecular Immunology; Molecular Genetics Of Cancer
Publisher's Version
https://doi.org/10.1038/ni.2545
Rights Notice
© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Creation Date: 2013-04-01 12:00:00
Last Modified: 0001-01-01 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙