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

• Published in: The Journal of experimental medicine Vol. 216; no. 4; pp. 884 - 899
• Main Authors: Qian, Liangyue, Bajana, Sandra, Georgescu, Constantin, Peng, Vincent, Wang, Hong-Cheng, Adrianto, Indra, Colonna, Marco, Alberola-Ila, Jose, Wren, Jonathan D, Sun, Xiao-Hong
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01.04.2019
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - 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; Transcription Factor 4 - metabolism; Transcription, Genetic; Transcriptome
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20182100

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.