Depletion of inflammatory dendritic cells with anti-CD209 conjugated to saporin toxin.
Monocytes rapidly infiltrate inflamed tissues and differentiate into CD209(+) inflammatory dendritic cells (DCs) that promote robust immunity or, if unregulated, inflammatory disease. Previous studies in experimental animal models indicate that inflammatory DC depletion through systemic elimination of their monocyte precursors with clodronate-loaded liposomes ameliorates the development of psoriasis and other diseases. However, translation of systemic monocyte depletion strategies is difficult due to the importance of monocytes during homeostasis and infection clearance. Here, we describe a strategy that avoids the monocyte intermediates to deplete inflammatory DCs through antibody-loaded toxin. Mice with an abundance of inflammatory DCs as a consequence of lipopolysaccharide exposure were treated with anti-CD209 antibody conjugated to saporin, a potent ribosome inactivator. The results demonstrate depletion of CD209(+) DCs. This strategy could prove useful for the targeted reduction of inflammatory DCs in disease.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Michael N
MN
Alonso
Josh G
JG
Gregorio
Matthew G
MG
Davidson
Joseph C
JC
Gonzalez
Edgar G
EG
Engleman
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D000922:Immunotoxins / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047589:Leukocyte Reduction Procedures; D051379:Mice; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1 / Q000276:immunology*; D000076985:Saporins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000922:Immunotoxins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin