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CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG
- Source :
- Journal of Experimental Medicine, 211(7), 1465-1483. Rockefeller University Press, Garcia-Vallejo, J J, Ilarregui, J M, Kalay, H, Chamorro, S, Koning, N, Unger, W W J, Ambrosini, M, Montserrat, V, Fernandes, R J, Bruijns, S C M, van Weering, J R T, Paauw, N J, O'Toole, T G, van Horssen, J, van der Valk, P, Nazmi, K, Bolscher, J G, Bajramovic, J, Dijkstra, C D, 't Hart, B A & van Kooyk, Y 2014, ' CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG ', Journal of Experimental Medicine, vol. 211, no. 7, pp. 1465-1483 . https://doi.org/10.1084/jem.20122192, Journal of Experimental Medicine, 211(7), 1457-1483. ROCKEFELLER UNIV PRESS, The Journal of Experimental Medicine, Garcia-Vallejo, J J, Ilarregui, J M, Kalay, H, Chamorro, S, Koning, N, Unger, W W, Ambrosini, M, Montserrat, V, Fernandes, R J, Bruijns, S C M, van Weering, J R T, Paauw, N J, O'Toole, T, van Horssen, J, van der Valk, P, Nazmi, K, Bolscher, J G M, Bajramovic, J, Dijkstra, C D, 't Hart, B A & van Kooyk, Y 2014, ' CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG ', Journal of Experimental Medicine, vol. 211, no. 7, pp. 1465-1483 . https://doi.org/10.1084/jem.20122192
- Publication Year :
- 2014
- Publisher :
- Rockefeller University Press, 2014.
-
Abstract
- Human myelin oligodendrocyte glycoprotein is decorated with fucosylated N-glycans that are recognized by DC-SIGN+ DCs and microglia that control immune homeostasis.<br />Myelin oligodendrocyte glycoprotein (MOG), a constituent of central nervous system myelin, is an important autoantigen in the neuroinflammatory disease multiple sclerosis (MS). However, its function remains unknown. Here, we show that, in healthy human myelin, MOG is decorated with fucosylated N-glycans that support recognition by the C-type lectin receptor (CLR) DC-specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN) on microglia and DCs. The interaction of MOG with DC-SIGN in the context of simultaneous TLR4 activation resulted in enhanced IL-10 secretion and decreased T cell proliferation in a DC-SIGN-, glycosylation-, and Raf1-dependent manner. Exposure of oligodendrocytes to proinflammatory factors resulted in the down-regulation of fucosyltransferase expression, reflected by altered glycosylation at the MS lesion site. Indeed, removal of fucose on myelin reduced DC-SIGN–dependent homeostatic control, and resulted in inflammasome activation, increased T cell proliferation, and differentiation toward a Th17-prone phenotype. These data demonstrate a new role for myelin glycosylation in the control of immune homeostasis in the healthy human brain through the MOG–DC-SIGN homeostatic regulatory axis, which is comprised by inflammatory insults that affect glycosylation. This phenomenon should be considered as a basis to restore immune tolerance in MS.
- Subjects :
- Male
Inflammasomes
Immune tolerance
Myelin
chemistry.chemical_compound
0302 clinical medicine
Cricetinae
Immunology and Allergy
BRAIN
IN-VIVO
GENE-EXPRESSION
0303 health sciences
biology
IMMUNE-RESPONSES
Inflammasome
MULTIPLE-SCLEROSIS
Interleukin-10
medicine.anatomical_structure
Female
Inflammation Mediators
medicine.drug
Fucosyltransferase
Glycosylation
T cell
Immunology
chemical and pharmacologic phenomena
Receptors, Cell Surface
CHO Cells
CERVICAL LYMPH-NODES
DENDRITIC CELLS
Article
C-TYPE LECTIN
Myelin oligodendrocyte glycoprotein
OLIGODENDROCYTE GLYCOPROTEIN
03 medical and health sciences
Cricetulus
SDG 3 - Good Health and Well-being
Immune Tolerance
medicine
Animals
Humans
Lectins, C-Type
Antigen-presenting cell
Cell Proliferation
030304 developmental biology
biochemical phenomena, metabolism, and nutrition
carbohydrates (lipids)
Proto-Oncogene Proteins c-raf
Toll-Like Receptor 4
nervous system
chemistry
T-CELLS
biology.protein
Th17 Cells
Myelin-Oligodendrocyte Glycoprotein
Cell Adhesion Molecules
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00221007
- Volume :
- 211
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....35fe3f682b0456d4e1e8cba037e27c29