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Lookup NU author(s): Dr Urszula Cytlak-ChaudhuriORCiD, Dr Anastasia ResteuORCiD, Professor Matthew CollinORCiD, Dr Venetia BigleyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The IRF8-dependent subset of classical dendritic cells (cDC), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor Flt3 ligand (Flt3L) yields very few cDC1 (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing Notch ligand Delta-like 1 (OP9-DL1) optimize Flt3L-driven development of cDC1 from murine immortalized progenitors and primary bone marrow cells. Co-culture with OP9-DL1 induced IRF8-dependent cDC1 with the phenotype (CD103+ Dec205+CD8+) and expression profile resembling primary splenic cDC1. OP9-DL1-induced cDC1 showed preferential migration towards Ccr7 ligands in vitro and superior T cell cross- priming and antitumor vaccination in vivo. Co-culture with OP9-DL1 also greatly increased the yield of IRF8-dependent CD141+ cDC1 from human bone marrow progenitors cultured with Flt3L. Thus, Notch signaling optimizes cDC generation in vitro and yields authentic cDC1 for functional studies and translational applications.
Author(s): Kirkling ME, Cytlak U, Lau CM, Lewis KL, Resteu A, Khodadadi-Jamayran A, Siebel CW, Salmon H, Merad M, Tsirigos A, Collin M, Bigley V, Reizis B
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2018
Volume: 23
Issue: 12
Pages: 3658-3672.e6
Print publication date: 19/06/2018
Online publication date: 19/06/2018
Acceptance date: 18/05/2018
Date deposited: 21/05/2018
ISSN (electronic): 2211-1247
Publisher: Cell Press
URL: https://doi.org/10.1016/j.celrep.2018.05.068
DOI: 10.1016/j.celrep.2018.05.068
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