Öppna denna publikation i ny flik eller fönster >>Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; School of Medicine, Shanghai University, Shanghai, China.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Medical Inflammation Research, MediCity Research Laboratory, University of Turku, Turku, Finland.
Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Department of Pharmacological & Technological Chemistry, I. M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.
Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, & Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, Frankfurt am Main, Germany; Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Medical Inflammation Research, Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Medical Inflammation Research, MediCity Research Laboratory, University of Turku, Turku, Finland.
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2025 (Engelska)Ingår i: Molecular Therapy, ISSN 1525-0016, E-ISSN 1525-0024Artikel i tidskrift (Refereegranskat) Epub ahead of print
Abstract [en]
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, cartilage damage, and bone erosion. Despite improvements with the introduction of biological disease-modifying anti-rheumatic drugs (DMARDs), RA remains an incurable life-long disease. Advancements in peptide-based vaccination may open new avenues for treating autoimmune diseases, including RA, by inducing immune tolerance while maintaining normal immune function. We have already demonstrated the efficacy of a potent vaccine against RA, consisting of the mouse major histocompatibility complex class II (Aq) protein bound to the immunodominant type II collagen peptide COL2259-273, which needed to be galactosylated at position 264. To translate the vaccine to humans and to further enhance vaccine efficacy, we modified the glycine residue at position 265 and conjugated it with the human DRB1∗04:01 molecule. Remarkably, this modified vaccine (named DR4-AL179) provided robust effectiveness in suppressing arthritis in DRB1∗04:01-expressing mice without the need for galactosylation at position 264. DR4-AL179 vaccination induces tolerance involving multiple immunoregulatory pathways, including the activation of V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA)-positive nonconventional regulatory T cells, which contribute to a potent suppressive response preventing arthritis development in mice. This modified RA vaccine offers a novel therapeutic potential for human autoimmune diseases.
Ort, förlag, år, upplaga, sidor
Elsevier, 2025
Nyckelord
COL2, immune checkpoints, MHCII, regulatory T cells, rheumatoid arthritis, T cell tolerance, tolerogenic, vaccine, VISTA
Nationell ämneskategori
Immunologi inom det medicinska området Reumatologi Autoimmunitet och inflammation
Identifikatorer
urn:nbn:se:umu:diva-238834 (URN)10.1016/j.ymthe.2025.04.034 (DOI)40285352 (PubMedID)2-s2.0-105004434061 (Scopus ID)
Forskningsfinansiär
Vetenskapsrådet, 2024-02575Novo Nordisk fondenKnut och Alice Wallenbergs Stiftelse, 2019.0059Stiftelsen Lars Hiertas MinneReumatikerförbundetKonung Gustaf V:s Jubileumsfond, SGI-2023-0993
2025-06-042025-06-042025-07-11