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J Exp Med. 2019 Apr 1;216(4):884-899. doi: 10.1084/jem.20182100. Epub 2019 Mar 21.

Suppression of ILC2 differentiation from committed T cell precursors by E protein transcription factors.

Author information

1
Oklahoma Medical Research Foundation, Program in Arthritis and Clinical Immunology, Oklahoma City, OK.
2
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO.
3
Department of Public Health Sciences, Henry Ford Health System, Detroit, MI.
4
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
5
Oklahoma Medical Research Foundation, Program in Arthritis and Clinical Immunology, Oklahoma City, OK sunx@omrf.org.
6
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.

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.

PMID:
30898894
PMCID:
PMC6446881
[Available on 2019-10-01]
DOI:
10.1084/jem.20182100

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