The transcription factor T-bet is essential for the development of NKp46(+) innate lymphocytes via the Notch pathway
- Author(s)
- Rankin, LC; Groom, JR; Chopin, M; Herold, MJ; Walker, JA; Mielke, LA; McKenzie, ANJ; Carotta, S; Nutt, SL; Belz, GT;
- 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
- Research Division(s)
- Molecular Immunology; Molecular Genetics Of Cancer
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076532/
- Publisher's Version
- https://doi.org/10.1038/ni.2545
- Terms of Use/Rights Notice
- © 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Creation Date: 2013-04-01 12:00:00