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Synthetically glycosylated antigens induce antigen-specific tolerance and prevent the onset of diabetes
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Synthetically glycosylated antigens induce antigen-specific tolerance and prevent the onset of diabetes
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Journal Article
Synthetically glycosylated antigens induce antigen-specific tolerance and prevent the onset of diabetes
2019
Overview
Homeostatic 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 T cells, 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.
Glycosylated peptides targeting hepatic antigen-presenting cells induce antigen-specific immune tolerance, preventing T-cell-mediated diabetes in mice.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/2
/ 13/21
/ 45/29
/ 64/60
/ Acetylgalactosamine - immunology
/ Acetylgalactosamine - pharmacology
/ Acetylglucosamine - immunology
/ Acetylglucosamine - pharmacology
/ Anergy
/ Animals
/ Antigen Presentation - drug effects
/ Antigen Presentation - immunology
/ Antigens
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ Diabetes
/ Diabetes Mellitus, Type 1 - drug therapy
/ Diabetes Mellitus, Type 1 - immunology
/ Female
/ Immune Tolerance - drug effects
/ Liver
/ Mice
/ Peptides
/ Spleen
