RT Journal Article
SR Electronic
T1 Platelet P-selectin initiates cross-presentation and dendritic cell differentiation in blood monocytes
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaaz1580
DO 10.1126/sciadv.aaz1580
VO 6
IS 11
A1 Han, Patrick
A1 Hanlon, Douglas
A1 Arshad, Najla
A1 Lee, Jung Seok
A1 Tatsuno, Kazuki
A1 Robinson, Eve
A1 Filler, Renata
A1 Sobolev, Olga
A1 Cote, Christine
A1 Rivera-Molina, Felix
A1 Toomre, Derek
A1 Fahmy, Tarek
A1 Edelson, Richard
YR 2020
UL http://advances.sciencemag.org/content/6/11/eaaz1580.abstract
AB 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 κB. 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.