Bigley V

Collin M

Cytlak U

Khodadadi-Jamayran A

Kirkling ME

Lau CM

Lewis KL

Merad M

Reizis B

Resteu A

Salmon H

Siebel CW

Tsirigos A

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

Newcastle University E-Prints

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Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells

Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells

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