Notch signaling schools thymic DCs

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Science  20 Oct 2017:
Vol. 358, Issue 6361, pp. 317-318
DOI: 10.1126/science.358.6361.317-f

Conventional and plasmacytoid dendritic cells in the thymus are important for the establishment of central tolerance. They induce autoreactive T cell death and generate regulatory T cells. Although these cells are believed to have an extrathymic origin, Martín-Gayo et al. uncovered evidence that human early thymic progenitors (ETPs) are another source. From postnatal thymocytes, ETPs differentiate into CD123+ common dendritic cell progenitors that can reconstitute dendritic cells in immunodeficient murine thymi. JAG1-mediated Notch signaling in medullary niches is critical for this process. The idea is that thymic progenitors, which escape strong Notch signaling via ligands such as DLL1 and DLL4 and then encounter JAG1, become myeloid-primed by up-regulating GATA2 and turning off GATA3.

J. Exp. Med. 10.1084/jem.20161564 (2017).

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