Dendritic cells modulate platelet activity in IVIg-mediated amelioration of ITP in mice.
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.
Huang
Hsuan-Shun
HS
Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan, Republic of China.
Sun
Der-Shan
DS
Lien
Te-Sheng
TS
Chang
Hsin-Hou
HH
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D051149:Selenoprotein P / Q000276:immunology / Q000378:metabolism
C499172:Fcgr2b protein, mouse; C485700:Fcgr3 protein, mouse; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; D051149:Selenoprotein P