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

Document Type

Article

Publication Date

4-1-2019

Publication Title

Journal of experimental medicine

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.

Medical Subject Headings

Animals; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism; Cell Differentiation/physiology; Cell Line; Interleukin-4/metabolism; Lung/cytology; Mice; Mice; Inbred C57BL; Mice; Knockout; Mice; Nude; Precursor Cells; T-Lymphoid/metabolism; Promyelocytic Leukemia Zinc Finger Protein/metabolism; Thymus Gland/cytology; Transcription Factor 4/genetics/metabolism; Transcription; Genetic; Transcriptome

PubMed ID

30898894

Volume

216

Issue

4

First Page

884

Last Page

899

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