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Suppression of ILC2 differentiation from committed T cell precursors by E protein transcription factors.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2019 Apr 01; Vol. 216 (4), pp. 884-899. Date of Electronic Publication: 2019 Mar 21. - Publication Year :
- 2019
-
Abstract
- Current models propose that group 2 innate lymphoid cells (ILC2s) are generated in the bone marrow. Here, we demonstrate that subsets of these cells can differentiate from multipotent progenitors and committed T cell precursors in the thymus, both in vivo and in vitro. These thymic ILC2s exit the thymus, circulate in the blood, and home to peripheral tissues. Ablation of E protein transcription factors greatly promotes the ILC fate while impairing B and T cell development. Consistently, a transcriptional network centered on the ZBTB16 transcription factor and IL-4 signaling pathway is highly up-regulated due to E protein deficiency. Our results show that ILC2 can still arise from what are normally considered to be committed T cell precursors, and that this alternative cell fate is restrained by high levels of E protein activity in these cells. Thymus-derived lung ILC2s of E protein-deficient mice show different transcriptomes, proliferative properties, and cytokine responses from wild-type counterparts, suggesting potentially distinct functions.<br /> (© 2019 Qian et al.)
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Cell Line
Interleukin-4 metabolism
Lung cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Nude
Promyelocytic Leukemia Zinc Finger Protein metabolism
Thymus Gland cytology
Transcription Factor 4 genetics
Transcription, Genetic
Transcriptome
Basic Helix-Loop-Helix Transcription Factors metabolism
Cell Differentiation physiology
Precursor Cells, T-Lymphoid metabolism
Transcription Factor 4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 216
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30898894
- Full Text :
- https://doi.org/10.1084/jem.20182100