期刊
NATURE BIOMEDICAL ENGINEERING
卷 3, 期 10, 页码 817-829出版社
NATURE PORTFOLIO
DOI: 10.1038/s41551-019-0424-1
关键词
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资金
- Whitaker Foundation
- School of Life Sciences, EPFL
- University of Chicago
- Juvenile Diabetes Research Foundation
- Anokion
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 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.
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