Neonatal platelets differentiate monocytes to a myeloid-derived suppressor cell phenotype
Preeti Maurya1, Daniel O'Reilly2, Zachary Hilt3
1Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY.
Insights
Neonatal platelets, unlike adult platelets, promote monocytes to become myeloid-derived suppressor cells (MDSCs) that limit T-cell activation. This immune-suppressing role of neonatal platelets may explain adverse outcomes from platelet transfusions in newborns.
Area of Science:
- Immunology
- Neonatal Medicine
- Hematology
Background:
- Adult and neonatal platelets differ in immune molecule expression.
- Predicting platelet-immune cell interactions in neonates is complex due to varying factors.
- Previous studies showed adult, but not neonatal, platelet transfusions increased monocyte trafficking in neonatal mice.
Purpose of the Study:
- To investigate the distinct immune effects of neonatal versus adult platelets on monocytes.
- To determine the mechanism by which neonatal platelets influence T-cell activation.
- To explore the implications of these findings for neonatal platelet transfusions.
Main Methods:
- Incubation of monocytes with neonatal or adult platelets/releasates.
- Assessment of monocyte phenotype (e.g., PD-L1 expression) and T-cell activation in vitro.
- In vivo studies using a neonatal mouse model and an asthma-like model.
- Analysis of prostaglandin E2 (PGE2) and EP4 signaling pathways.
Main Results:
- Neonatal platelets, but not adult platelets, induced a myeloid-derived suppressor cell (MDSC) phenotype in monocytes.
- MDSCs generated by neonatal platelets exhibited increased PD-L1 expression.
- Monocytes pre-incubated with neonatal platelets or releasates suppressed T-cell activation both in vitro and in vivo.
- Neonatal platelet-induced immune suppression was mediated by increased PGE2 production signaling through monocyte EP4 receptors.
Conclusions:
- Neonatal platelets possess immune-limiting functions in the neonatal period by suppressing T-cell responses indirectly.
- These findings suggest a mechanism contributing to adverse outcomes observed with neonatal platelet transfusions.
- Understanding these distinct platelet functions is crucial for optimizing neonatal care.
Abstract:
Adult platelets are relatively enriched in immune-related molecules compared with neonatal platelets, but neonatal platelets express some growth factors and enzymes at comparatively higher levels. This makes a prediction of platelet-immune cell interaction outcomes in neonates a challenge, as they are likely dependent on the cell type and tissue environment at the time of injury or infection. Our previous studies revealed that the transfusion of adult but not neonatal platelets into thrombocytopenic neonatal mice led to an acute increase in monocyte trafficking. We have now found that neonatal but not adult platelets induce monocytes to a myeloid-derived suppressor cell phenotype, typified by increased programmed death ligand 1, that limits T-cell activation in vitro and in vivo. Monocytes previously incubated with neonatal but not adult platelets or platelet releasates limited T-cell activation in vitro. Using an in vivo asthma-like model we also found that the treatment of mice with monocytes before incubation with neonatal platelet releasates limited T-cell activation in a asthma-like model. Platelet-driven effects were dependent on neonatal platelets producing more prostaglandin E2 that signaled through monocyte prostaglandin EP4 receptor. These studies indicate that neonatal platelets have immune-limiting roles in the postnatal period by indirectly limiting T-cell responses, perhaps contributing to the adverse outcomes of platelet transfusions to neonates.
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