title: Augmenting DAF levels in vivo ameliorates experimental autoimmune encephalomyelitis.
abstract: Recent studies in experimental autoimmune encephalomyelitis (EAE) have found that CNS injury in Daf1(-/-) mice is much greater than in wild types (WTs), suggesting that upregulating DAF levels in vivo might ameliorate disease. To test this, we generated a Daf1 transgenic (Tg) mouse which had elevated DAF levels on its cell surfaces. In by-stand C3b uptake assays, Daf1 Tg mouse erythrocytes took up less C3b on their surfaces than WT erythrocytes. When co-cultured with OT-II CD4(+) T cells together with OVA(323-339) peptide, Daf1 Tg mouse bone marrow derived dendritic cells (BM-DCs) produced less C5a and C3a than WT BM-DCs and stimulated a lesser T cell response. In MOG(35-55) immunization induced EAE model, Daf1 Tg mice exhibited delayed disease onset and decreased clinical scores compared to WTs. Histological analyses showed that there were less inflammation and demyelination in spinal cords in Daf1 Tg mice than those in WTs. In accordance with these results, Daf1 Tg mice had decreased MOG(35-55) specific Th1 and Th17 responses. These data provide further evidence that DAF suppresses autoreactive T cell responses in EAE, and indicate that augmenting its expression levels could be effective therapeutically in treating multiple sclerosis as well as other T cell mediated diseases.
authors: Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA.
authors: Qing
authors: Q
authors: Li
authors: Danping
authors: D
authors: Huang
authors: Kristine
authors: K
authors: Nacion
authors: Hong
authors: H
authors: Bu
authors: Feng
authors: F
authors: Lin
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015926:Complement C3a / Q000276:immunology* / Q000378:metabolism; D015936:Complement C5a / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D018958:CD55 Antigens; D006023:Glycoproteins; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; C111390:OVA 323-339; D010446:Peptide Fragments; C521184:decay-accelerating factor 1, mouse; C445081:myelin oligodendrocyte glycoprotein (35-55); D015926:Complement C3a; D015936:Complement C5a; D007371:Interferon-gamma; D010047:Ovalbumin