PMID:24935259

Citation	García-Vallejo, JJ, Ilarregui, JM, Kalay, H, Chamorro, S, Koning, N, Unger, WW, Ambrosini, M, Montserrat, V, Fernandes, RJ, Bruijns, SC, van Weering, JR, Paauw, NJ, O'Toole, T, van Horssen, J, van der Valk, P, Nazmi, K, Bolscher, JG, Bajramovic, J, Dijkstra, CD, 't Hart, BA and van Kooyk, Y (2014) CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG. J. Exp. Med. 211:1465-83
Abstract	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.
Links	PubMed PMC4076586 Online version:10.1084/jem.20122192
Keywords	Animals; Brain/cytology; Brain/immunology; CHO Cells; Cell Adhesion Molecules/genetics; Cell Adhesion Molecules/immunology; Cell Proliferation; Cricetinae; Cricetulus; Female; Humans; Immune Tolerance/physiology; Inflammasomes/genetics; Inflammasomes/immunology; Inflammation Mediators/immunology; Interleukin-10/genetics; Interleukin-10/immunology; Lectins, C-Type/genetics; Lectins, C-Type/immunology; Male; Myelin-Oligodendrocyte Glycoprotein/genetics; Myelin-Oligodendrocyte Glycoprotein/immunology; Proto-Oncogene Proteins c-raf/genetics; Proto-Oncogene Proteins c-raf/immunology; Receptors, Cell Surface/genetics; Receptors, Cell Surface/immunology; Th17 Cells/cytology; Th17 Cells/immunology; Toll-Like Receptor 4/genetics; Toll-Like Receptor 4/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:S10A8		GO:0010543: regulation of platelet activation	ECO:0000314:		P		As seen in Figure 1D, WT mice had platelet accumulation after 30 seconds of being previously injured by a laser.	complete CACAO 10667

References

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