Characterization of relapsing autoimmune encephalomyelitis and its treatment with decoy chemokine receptor genes.
To elucidate the pathomechanisms of relapses of autoimmune disorders and to develop immunotherapy against relapses, we induced acute monophasic and chronic relapsing (CR) experimental autoimmune encephalomyelitis (EAE) in DA rats. Immunopathological and cytokine-chemokine analyses demonstrated that the number of infiltrating macrophages was significantly elevated in the CR-EAE than in acute EAE lesions and that IFN-gamma and IP-10 in the spinal cord were significantly upregulated during the first attack and relapse of CR-EAE, respectively, than at the peak of acute EAE. In vivo administration of decoy chemokine receptor plasmid DNAs encoding the binding sites of CXCR3 and CCR2 suppressed the development of relapse of CR-EAE. Importantly, multiple injections of DNAs did not elicit the antibody production against chemokine receptors. Taken together, these findings demonstrated that neutralization therapy with decoy chemokine receptor DNAs is effective to control autoimmune diseases.
Matsumo
Yoh
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo 183-8526, Japan. matyoh@tmin.ac.jp
Sakuma
Hiroshi
H
Miyakoshi
Akira
A
Tsukada
Yukiko
Y
Kohyama
Kuniko
K
Park
Il-Kwon
IK
Tanuma
Naoyuki
N
D000208:Acute Disease; D000818:Animals; D000941:Antigens / Q000502:physiology; D002465:Cell Movement; D049109:Cell Proliferation; D002490:Central Nervous System / Q000473:pathology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000627:therapeutic use; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D015316:Genetic Therapy; D007114:Immunization; D007167:Immunotherapy; D008264:Macrophages / Q000473:pathology; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019707:Receptors, Chemokine / Q000235:genetics*; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D000941:Antigens; D018925:Chemokines; D016207:Cytokines; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D004247:DNA