Sialic acid-modified antigens impose tolerance via inhibition of T-cell proliferation and de novo induction of regulatory T cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/609581
Title:
Sialic acid-modified antigens impose tolerance via inhibition of T-cell proliferation and de novo induction of regulatory T cells.
Authors:
Perdicchio, Maurizio; Ilarregui, Juan M; Verstege, Marleen I; Cornelissen, Lenneke A M; Schetters, Sjoerd T T; Engels, Steef; Ambrosini, Martino; Kalay, Hakan; Veninga, Henrike; den Haan, Joke M M; van Berkel, Lisette A; Samsom, Janneke N; Crocker, Paul R; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Berod, Luciana; Garcia-Vallejo, Juan J; van Kooyk, Yvette; Unger, Wendy W J
Abstract:
Sialic 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.
Affiliation:
Twincore, Institute for Experimental Virology, Hannover, Germany.
Citation:
Sialic 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.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
22-Mar-2016
URI:
http://hdl.handle.net/10033/609581
DOI:
10.1073/pnas.1507706113
PubMed ID:
26941238
Type:
Article
Language:
en
ISSN:
1091-6490
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorPerdicchio, Maurizioen
dc.contributor.authorIlarregui, Juan Men
dc.contributor.authorVerstege, Marleen Ien
dc.contributor.authorCornelissen, Lenneke A Men
dc.contributor.authorSchetters, Sjoerd T Ten
dc.contributor.authorEngels, Steefen
dc.contributor.authorAmbrosini, Martinoen
dc.contributor.authorKalay, Hakanen
dc.contributor.authorVeninga, Henrikeen
dc.contributor.authorden Haan, Joke M Men
dc.contributor.authorvan Berkel, Lisette Aen
dc.contributor.authorSamsom, Janneke Nen
dc.contributor.authorCrocker, Paul Ren
dc.contributor.authorSparwasser, Timen
dc.contributor.authorBerod, Lucianaen
dc.contributor.authorGarcia-Vallejo, Juan Jen
dc.contributor.authorvan Kooyk, Yvetteen
dc.contributor.authorUnger, Wendy W Jen
dc.date.accessioned2016-05-17T14:22:13Zen
dc.date.available2016-05-17T14:22:13Zen
dc.date.issued2016-03-22en
dc.identifier.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.en
dc.identifier.issn1091-6490en
dc.identifier.pmid26941238en
dc.identifier.doi10.1073/pnas.1507706113en
dc.identifier.urihttp://hdl.handle.net/10033/609581en
dc.description.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.en
dc.language.isoenen
dc.titleSialic acid-modified antigens impose tolerance via inhibition of T-cell proliferation and de novo induction of regulatory T cells.en
dc.typeArticleen
dc.contributor.departmentTwincore, Institute for Experimental Virology, Hannover, Germany.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen

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