Inhibiting the P2Y Receptor in Megakaryocytes and Platelets Suppresses Interferon-Associated Responses.

The authors investigated the impact of antiplatelet therapy on the megakaryocyte (MK) and platelet transcriptome. RNA-sequencing was performed on MKs treated with aspirin or P2Y inhibitor, platelets from healthy volunteers receiving aspirin or P2Y inhibition, and platelets from patients with systemic lupus erythematosus (SLE). P2Y inhibition reduced gene expression and inflammatory pathways in MKs and platelets. In SLE, the interferon (IFN) pathway was elevated. In vitro experiments demonstrated the role of P2Y inhibition in reducing IFNα-induced platelet-leukocyte interactions and IFN signaling pathways. These results suggest that P2Y inhibition may have therapeutic potential for proinflammatory and autoimmune conditions like SLE.