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Contenuto archiviato il 2024-06-18

Reinforcement of tolerance to myelin antigens, a preclinical study in the common marmoset model of autoimmune encephalomyelitis

Obiettivo

The autoimmune disease sclerosis multiple (MS) induces neuronal demyelinitation caused among others by autoantibodies. A significant proportion of them are directed against the myelin/oligodendrocyte glycoprotein (MOG). The suppression of anti-MOG autoimmunity should be an essential component of a therapy for MS. Common marmoset provide us a unique pre-clinical model due to its high similarity to human and the resemblance of marmoset experimental autoimmune encephalitis (EAE) to MS. Immature dendritic cells (DC) control peripheral tolerance to self antigens through the balance between the signals provided by ligands of their C-type lectins receptors (CLR) and Toll-like receptors (TLR). The disturbed glycosylation of MOG derange the union to CLR and promote autoimmune reaction. Targeting properly glycosilated MOG to CLR, tolerance antigen specific can be induced.

The native or tailor-made glycosylated recombinant marmoset MOG (rmMOGgly) will be used for tolerization, whereas unglycosylated MOG (rmMOG) will be used for EAE induction. We will preferentially focus on the specific CLR DC-SIGN, expressed in immature DC. Tolerance to rmMOGgly would be promoted by preventing the DC maturation. As a main consequence, marmosets immunized with rmMOGgly would be protected to EAE disease in this pre-clinical model. Working in the proposed project will contribute to my professional growth since I will gain access to applied science when my previous research experience was mainly based on basic science. It is also a challenge to work in Molecular Biology.

Invito a presentare proposte

FP6-2002-MOBILITY-5
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Coordinatore

RESEARCH INSTITUTE OF IMMUNOLOGY AND INFLAMMATORY DISEASES/VRIJE UNIVERSITY MEDICAL CENTER
Contributo UE
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Indirizzo


Paesi Bassi

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