1. Suppression of ILC2 differentiation from committed T cell precursors by E protein transcription factors
- Author
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Xiao Hong Sun, Liangyue Qian, Sandra Bajana, Jonathan D. Wren, Hong Cheng Wang, Indra Adrianto, Marco Colonna, Vincent Peng, José Alberola-Ila, and Constantin Georgescu
- Subjects
Transcription, Genetic ,medicine.medical_treatment ,T cell ,Immunology ,Mice, Nude ,Thymus Gland ,Biology ,Cell fate determination ,Article ,Cell Line ,Mice ,03 medical and health sciences ,Transcription Factor 4 ,0302 clinical medicine ,Precursor cell ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Animals ,Immunology and Allergy ,Promyelocytic Leukemia Zinc Finger Protein ,Progenitor cell ,Lung ,Transcription factor ,Research Articles ,030304 developmental biology ,Mice, Knockout ,Precursor Cells, T-Lymphoid ,0303 health sciences ,Innate lymphoid cell ,Cell Differentiation ,Cell biology ,Mice, Inbred C57BL ,Cytokine ,medicine.anatomical_structure ,Interleukin-4 ,Signal transduction ,Transcriptome ,030215 immunology - Abstract
Qian et al. shows that ILC2s can be generated from not only thymic multipotent progenitors but also committed T cell precursors. These processes are greatly suppressed by E protein transcription factors. Thymic ILC2s show functional differences from those made elsewhere., 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., Graphical Abstract
- Published
- 2019