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

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.

Source: The Journal of Experimental Medicine - March 31, 2019 Category: Internal Medicine Authors: Qian, L., Bajana, S., Georgescu, C., Peng, V., Wang, H.-C., Adrianto, I., Colonna, M., Alberola-Ila, J., Wren, J. D., Sun, X.-H. Tags: Articles Source Type: research