| First Author | Kirkling ME | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 12 | Pages | 3658-3672.e6 |
| PubMed ID | 29925006 | Mgi Jnum | J:271629 |
| Mgi Id | MGI:6279043 | Doi | 10.1016/j.celrep.2018.05.068 |
| Citation | Kirkling ME, et al. (2018) Notch Signaling Facilitates In Vitro Generation of Cross-Presenting Classical Dendritic Cells. Cell Rep 23(12):3658-3672.e6 |
| abstractText | 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(+) CD8alpha(+)) 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. |
