Intravenous immunoglobulin (IVIg) is an effective treatment against immune thrombocytopenia (ITP). Previous studies suggested that IVIg exerts this ameliorative role through 2 different leukocyte subsets. Dendritic cells (DCs) modulate the immunosuppression in an adoptive cell transfer model, and phagocytes up-regulate their inhibitory IgG Fc receptors (FcγR)IIB expression and thereby ameliorate the inflammatory response and platelet clearance. However, whether or not regulatory mechanisms exist among DCs, phagocytes, and platelets is still largely unknown. In this study we present findings that IVIg-primed splenic CD11c(+) DCs (IVIg-DCs) primarily mediate their anti-inflammatory effects at the level of the platelet rather than the phagocyte. IVIg-DCs did not ameliorate ITP in Fcgr2b(-/-), Fcgr3(-/-), nor P-Selp(-/-) mice, implicating the potential involvement of these pathways in IVIg action. As platelets are a component of DC regulatory circuits, these findings may suggest an alternative perspective for the use of IVIg treatment.