Wilson, D. ScottDamo, MartinaHirosue, SachikoRaczy, Michal M.Bruenggel, KymDiaceri, GiacomoQuaglia-Thermes, XavierHubbell, Jeffrey A.2019-10-202019-10-202019-10-202019-10-0110.1038/s41551-019-0424-1https://infoscience.epfl.ch/handle/20.500.14299/162117WOS:000489154800011Homeostatic antigen presentation by hepatic antigen-presenting cells, which results in tolerogenic T-cell education, could be exploited to induce antigen-specific immunological tolerance. Here we show that antigens modified with polymeric forms of either N-acetylgalactosamine or N-acetylglucosamine target hepatic antigen-presenting cells, increase their antigen presentation and induce antigen-specific tolerance, as indicated by CD4(+) and CD8(+) T-cell deletion and anergy. These synthetically glycosylated antigens also expanded functional regulatory Tcells, which are necessary for the durable suppression of antigen-specific immune responses. In an adoptive-transfer mouse model of type-1 diabetes, treatment with the glycosylated autoantigens prevented T-cell-mediated diabetes, expanded antigen-specific regulatory T cells and resulted in lasting tolerance to a subsequent challenge with activated diabetogenic T cells. Glycosylated autoantigens targeted to hepatic antigen-presenting cells might enable therapies that promote immune tolerance in patients with autoimmune diseases.Engineering, BiomedicalEngineeringsinusoidal endothelial-cellsregulatory t-cellsgrowth-factor-betac-type lectinasialoglycoprotein receptormannose receptorcross-presentationkupffer cellsrat-liverin-vitrotext::journal::journal article::research article