First Author | Han P | Year | 2020 |
Journal | Sci Adv | Volume | 6 |
Issue | 11 | Pages | eaaz1580 |
PubMed ID | 32195350 | Mgi Jnum | J:297993 |
Mgi Id | MGI:6479488 | Doi | 10.1126/sciadv.aaz1580 |
Citation | Han P, et al. (2020) Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes. Sci Adv 6(11):eaaz1580 |
abstractText | Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen-specific immunity. Clinically, however, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited success. We hypothesized that DCs produced in a physiological manner may be more effective and found that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18 hours) maturation into physiological DCs (phDCs). Differentiation of monocytes into phDCs was concomitant with the formation of an "adhesion synapse," a biophysical junction enriched with platelet P-selectin and monocyte P-selectin glycoprotein ligand 1, followed by intracellular calcium fluxing and nuclear localization of nuclear factor kappaB. phDCs were more efficient than cytokine-derived DCs in generating tumor-specific T cell immunity. Our findings demonstrate that platelets mediate a cytokine-independent, physiologic maturation of DC and suggest a novel strategy for DC-based immunotherapies. |