Synthetically glycosylated antigens for the antigen-specific suppression of established immune responses.

Animals Mice Immune Tolerance Autoimmunity Glycosylation Acetylgalactosamine Encephalomyelitis, Autoimmune, Experimental / therapy

Journal

Nature biomedical engineering
ISSN: 2157-846X
Titre abrégé: Nat Biomed Eng
Pays: England
ID NLM: 101696896

Informations de publication

Date de publication:
09 2023
Historique:
received: 23 08 2022
accepted: 02 08 2023
medline: 25 9 2023
pubmed: 8 9 2023
entrez: 7 9 2023
Statut: ppublish

Résumé

Inducing antigen-specific tolerance during an established immune response typically requires non-specific immunosuppressive signalling molecules. Hence, standard treatments for autoimmunity trigger global immunosuppression. Here we show that established antigen-specific responses in effector T cells and memory T cells can be suppressed by a polymer glycosylated with N-acetylgalactosamine (pGal) and conjugated to the antigen via a self-immolative linker that allows for the dissociation of the antigen on endocytosis and its presentation in the immunoregulatory environment. We show that pGal-antigen therapy induces antigen-specific tolerance in a mouse model of experimental autoimmune encephalomyelitis (with programmed cell-death-1 and the co-inhibitory ligand CD276 driving the tolerogenic responses), as well as the suppression of antigen-specific responses to vaccination against a DNA-based simian immunodeficiency virus in non-human primates. Our findings show that pGal-antigen therapy invokes mechanisms of immune tolerance to resolve antigen-specific inflammatory T-cell responses and suggest that the therapy may be applicable across autoimmune diseases.

Identifiants

DOI: 10.1038/s41551-023-01086-2 PMID: 37679570
pubmed: 37679570
doi: 10.1038/s41551-023-01086-2
pii: 10.1038/s41551-023-01086-2
doi:

Substances chimiques

Acetylgalactosamine KM15WK8O5T

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1142-1155

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR000430
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014599
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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Auteurs

Andrew C Tremain (AC)

Committee on Immunology, University of Chicago, Chicago, IL, USA.

Rachel P Wallace (RP)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.
ORCID: 0000-0003-4439-1173

Kristen M Lorentz (KM)

Anokion US Inc., Cambridge, MA, USA.

Thomas B Thornley (TB)

Anokion US Inc., Cambridge, MA, USA.

Jennifer T Antane (JT)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.

Michal R Raczy (MR)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.

Joseph W Reda (JW)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.
ORCID: 0000-0002-9413-5111

Aaron T Alpar (AT)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.
ORCID: 0000-0003-4669-4813

Anna J Slezak (AJ)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.

Elyse A Watkins (EA)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.
ORCID: 0000-0003-2691-5930

Chitavi D Maulloo (CD)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.

Erica Budina (E)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA.

Ani Solanki (A)

Animal Resources Center, University of Chicago, Chicago, IL, USA.

Mindy Nguyen (M)

Animal Resources Center, University of Chicago, Chicago, IL, USA.

David J Bischoff (DJ)

Anokion US Inc., Cambridge, MA, USA.

Jamie L Harrington (JL)

Anokion US Inc., Cambridge, MA, USA.

Rabinarayan Mishra (R)

Anokion US Inc., Cambridge, MA, USA.

Gregory P Conley (GP)

Anokion US Inc., Cambridge, MA, USA.

Romain Marlin (R)

Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France.
ORCID: 0000-0001-8932-0171

Nathalie Dereuddre-Bosquet (N)

Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France.

Anne-Sophie Gallouët (AS)

Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France.

Roger LeGrand (R)

Center for Immunology of Viral, Auto-immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, INSERM, CEA, Fontenay-aux-Roses, France.

D Scott Wilson (DS)

Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA. scott.wilson@jhmi.edu.
Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA. scott.wilson@jhmi.edu.
ORCID: 0000-0001-8029-1036

Stephan Kontos (S)

Anokion US Inc., Cambridge, MA, USA.

Jeffrey A Hubbell (JA)

Committee on Immunology, University of Chicago, Chicago, IL, USA. jhubbell@uchicago.edu.
Pritzker School for Molecular Engineering, University of Chicago, Chicago, IL, USA. jhubbell@uchicago.edu.
Committee on Cancer Biology, University of Chicago, Chicago, IL, USA. jhubbell@uchicago.edu.
ORCID: 0000-0003-0276-5456

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Synthetically glycosylated antigens for the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Synthetically glycosylated antigens for the...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunomodulation › Tolérance immunitaire › Synthetically glycosylated antigens for the...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Auto-immunité › Synthetically glycosylated antigens for the...
questionsmedicales.fr › Métabolisme › Métabolisme glucidique › Glycosylation › Synthetically glycosylated antigens for the...
questionsmedicales.fr › Glucides › Osamines › Hexosamine › Galactosamine › Acétyl-galactosamine › Synthetically glycosylated antigens for the...
questionsmedicales.fr › Techniques d'investigation › Modèles animaux › Maladie neurologique auto-immune expérimentale › Encéphalomyélite auto-immune expérimentale › Synthetically glycosylated antigens for the...