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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

Margaret E Kirkling, Urszula Cytlak, Colleen M Lau, Kanako L Lewis, Anastasia Resteu, Alireza Khodadadi-Jamayran, Christian W Siebel, Hélène Salmon, Miriam Merad, Aristotelis Tsirigos, Matthew Collin, Venetia Bigley, etc.

Cell Rep. 2018 Jun 19;23(12):3658-3672.e6.

PMID: 29925006

Abstract:

The IRF8-dependent subset of classical dendritic cells (cDCs), 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 cDC1s (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing the Notch ligand Delta-like 1 (OP9-DL1) optimize FLT3L-driven development of cDC1s from murine immortalized progenitors and primary bone marrow cells. Co-culture with OP9-DL1 induced IRF8-dependent cDC1s with a phenotype (CD103+ Dec205+ CD8α+) and expression profile resembling primary splenic cDC1s. OP9-DL1-induced cDC1s showed preferential migration toward 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+ cDC1s from human bone marrow progenitors cultured with FLT3L. Thus, Notch signaling optimizes cDC generation in vitro and yields authentic cDC1s for functional studies and translational applications.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248805	flt3-Ligand from mouse			Price

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