CNS myelin induces regulatory functions of DC-SIGN-expressing, antigen-presenting cells via cognate interaction with MOG

J.J. Garcia-Vallejo, J.M. Ilarregui, H. Kalay, S. Chamorro, N. Koning, W.W.J. Unger, M. Ambrosini, V. Montserrat, R.J. Fernandes, S.C.M. Bruijns, J.R.T. van Weering, N.J. Paauw, T.G. O'Toole, J. van Horssen, P. van der Valk, K. Nazmi, J.G. Bolscher, J. Bajramovic, C.D. Dijkstra, B.A. 't HartY. van Kooyk

Research output: Contribution to JournalArticleAcademicpeer-review

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 Th
Original languageEnglish
Pages (from-to)1465-1483
JournalJournal of Experimental Medicine
Volume211
Issue number7
DOIs
Publication statusPublished - 2014

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