| First Author | Ferreira ACF | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 2 | Pages | 166-178 |
| PubMed ID | 33432227 | Mgi Jnum | J:305262 |
| Mgi Id | MGI:6705767 | Doi | 10.1038/s41590-020-00833-w |
| Citation | Ferreira ACF, et al. (2021) RORalpha is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus. Nat Immunol 22(2):166-178 |
| abstractText | Type 2 innate lymphoid cells (ILC2) contribute to immune homeostasis, protective immunity and tissue repair. Here we demonstrate that functional ILC2 cells can arise in the embryonic thymus from shared T cell precursors, preceding the emergence of CD4(+)CD8(+) (double-positive) T cells. Thymic ILC2 cells migrated to mucosal tissues, with colonization of the intestinal lamina propria. Expression of the transcription factor RORalpha repressed T cell development while promoting ILC2 development in the thymus. From RNA-seq, assay for transposase-accessible chromatin sequencing (ATAC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) data, we propose a revised transcriptional circuit to explain the co-development of T cells and ILC2 cells from common progenitors in the thymus. When Notch signaling is present, BCL11B dampens Nfil3 and Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORalpha overrides the repression of Nfil3 and Id2 repression, allowing ID2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORalpha expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus. |
