Sialic acid-modified antigens impose tolerance via inhibition of T-cell proliferation and de novo induction of regulatory T cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Ilarregui, Juan M
Verstege, Marleen I
Cornelissen, Lenneke A M
Schetters, Sjoerd T T
den Haan, Joke M M
van Berkel, Lisette A
Samsom, Janneke N
Crocker, Paul R
Garcia-Vallejo, Juan J
van Kooyk, Yvette
Unger, Wendy W J
MetadataShow full item record
AbstractSialic acids are negatively charged nine-carbon carboxylated monosaccharides that often cap glycans on glycosylated proteins and lipids. Because of their strategic location at the cell surface, sialic acids contribute to interactions that are critical for immune homeostasis via interactions with sialic acid-binding Ig-type lectins (siglecs). In particular, these interactions may be of importance in cases where sialic acids may be overexpressed, such as on certain pathogens and tumors. We now demonstrate that modification of antigens with sialic acids (Sia-antigens) regulates the generation of antigen-specific regulatory T (Treg) cells via dendritic cells (DCs). Additionally, DCs that take up Sia-antigen prevent formation of effector CD4(+)and CD8(+)T cells. Importantly, the regulatory properties endowed on DCs upon Sia-antigen uptake are antigen-specific: only T cells responsive to the sialylated antigen become tolerized. In vivo, injection of Sia-antigen-loaded DCs increased de novo Treg-cell numbers and dampened effector T-cell expansion and IFN-γ production. The dual tolerogenic features that Sia-antigen imposed on DCs are Siglec-E-mediated and maintained under inflammatory conditions. Moreover, loading DCs with Sia-antigens not only inhibited the function of in vitro-established Th1 and Th17 effector T cells but also significantly dampened ex vivo myelin-reactive T cells, present in the circulation of mice with experimental autoimmune encephalomyelitis. These data indicate that sialic acid-modified antigens instruct DCs in an antigen-specific tolerogenic programming, enhancing Treg cells and reducing the generation and propagation of inflammatory T cells. Our data suggest that sialylation of antigens provides an attractive way to induce antigen-specific immune tolerance.
CitationSialic acid-modified antigens impose tolerance via inhibition of T-cell proliferation and de novo induction of regulatory T cells. 2016, 113 (12):3329-34 Proc. Natl. Acad. Sci. U.S.A.
AffiliationTwincore, Institute for Experimental Virology, Hannover, Germany.
The following license files are associated with this item:
- CD8+ dendritic cell-mediated tolerance of autoreactive CD4+ T cells is deficient in NOD mice and can be corrected by blocking CD40L.
- Authors: Price JD, Beauchamp NM, Rahir G, Zhao Y, Rieger CC, Lau-Kilby AW, Tarbell KV
- Issue date: 2014 Feb
- Increased alpha2,6-sialylation of surface proteins on tolerogenic, immature dendritic cells and regulatory T cells.
- Authors: Jenner J, Kerst G, Handgretinger R, Müller I
- Issue date: 2006 Sep
- Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation.
- Authors: Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S
- Issue date: 2008 Jul 22
- Dendritic cells induce regulatory T cell proliferation through antigen-dependent and -independent interactions.
- Authors: Zou T, Caton AJ, Koretzky GA, Kambayashi T
- Issue date: 2010 Sep 1
- Intestinal epithelial cell-derived integrin αβ6 plays an important role in the induction of regulatory T cells and inhibits an antigen-specific Th2 response.
- Authors: Chen X, Song CH, Feng BS, Li TL, Li P, Zheng PY, Chen XM, Xing Z, Yang PC
- Issue date: 2011 Oct