Depletion of folate-receptor-positive macrophages leads to alleviation of symptoms and prolonged survival in two murine models of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease involving deposition of immune complexes in normal tissues and the consequent accumulation of immune cells and tissue injury. Activated macrophages are thought to contribute to disease pathogenesis by releasing inflammatory mediators that both cause direct tissue damage and attract other immune cells that augment inflammation. Previous studies in animal models of rheumatoid arthritis have shown that activated macrophages express a folate receptor that can be targeted with folate-linked haptens, leading to (1) marking of the activated macrophages with highly immunogenic haptens, (2) recognition of the marked cells by Fc receptor-expressing immune cells, and (3) destruction of the antibody-coated macrophages by the body's own immune system. Here we demonstrate that the same folate-hapten-targeted immunotherapy can greatly suppress symptoms of SLE in two animal models of the disease, resulting in reduced immune complex deposition, diminished damage to normal tissues, and prolonged animal survival.
Varghese
Bindu
B
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Haase
Nicholas
N
Low
Philip S
PS
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D004195:Disease Models, Animal; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D007668:Kidney; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015996:Survival Rate
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D005492:Folic Acid