TY - JOUR
T1 - Suppression of ILC2 differentiation from committed T cell precursors by E protein transcription factors
AU - Qian, Liangyue
AU - Bajana, Sandra
AU - Georgescu, Constantin
AU - Peng, Vincent
AU - Wang, Hong Cheng
AU - Adrianto, Indra
AU - Colonna, Marco
AU - Alberola-Ila, Jose
AU - Wren, Jonathan D.
AU - Sun, Xiao Hong
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (1R01AI126851) and the Presbyterian Health Foundation to X.-H. Sun. X.-H. Sun holds the Lew and Myra Ward Chair in Biomedical Research at the Oklahoma Medical Research Foundation. The authors declare no competing financial interests.
Publisher Copyright:
© 2019 Qian et al.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064143049&partnerID=8YFLogxK
U2 - 10.1084/jem.20182100
DO - 10.1084/jem.20182100
M3 - Article
C2 - 30898894
AN - SCOPUS:85064143049
SN - 0022-1007
VL - 216
SP - 884
EP - 899
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -