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C-type lectin : glycoprotein interactions in the central nervous system;...

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Title C-type lectin : glycoprotein interactions in the central nervous system; homeostatic and pathogenic mechanisms in neuroinflammatory diseases
Period 10 / 2007 - 10 / 2010
Status Completed
Research number OND1331463
Data Supplier Stichting MS Research

Abstract

Antigen presenting cells (APC) are equipped with a variety of receptors for the binding and internalization of antigens, including Toll-like receptors (TLR) that recognize conserved pathogen-associated molecular patterns (PAMPS) and C-type lectin receptors (CLR) that recognize carbohydrate epitopes present on self antigens and pathogens. It has been well established that APC are instrumental in the onset of inflammatory responses but at the same time can have a potent tolerogenic function. While much is known about the regulation of APC functions in the periphery by CLR/TLR interaction it is unclear whether such mechanisms are effective in the central nervous system (CNS) and whether disturbance of these mechanisms set the stage for the initiation and/or perpetuation of CNS inflammation in MS. However, several in vivo models have demonstrated that CLR/TLR targeting of antigens can either induce or restore auto-immunity by inducing antigen specific tolerance. In our pilot experiments we have demonstrated that CLR expression (DC-SIGN and MGL) is highly regulated on APC in healthy and MS diseased brain such as resident APC like microglia and residente and infiltrating APC such as perivascular macrophages. Moreover glycan structures recognized by these CLR expressing APC are also expressed within myelin. In this project we will further investigate how biological functions of CLR expressing dendritic cells (DC) and glycan modified MOG can be applied to influence the regulatory role of DC in the maintenance of immune tolerance. We will integrate human in vitro studies and murine EAE models using CLR- transgenic and knock-out mice as well as glycosyltransferase knock-out mice.

Related organisations

Related people

Researcher J.J. Garcia-Vellejo
Project leader Prof.dr. Y. van Kooyk

Classification

D21800 Immunology, serology
D23230 Neurology, otorhinolaryngology, opthalmology

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