Tolerogenic antigen-specific vaccine induces VISTA-enriched regulatory T cells and protects against arthritis in DRB1∗04:01 mice
Year: 2025
Type: article
Abstract: , 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.
Source: Molecular Therapy
Authors: Laura Romero-Castillo, Rajan Kumar Pandey, Bingze Xu, Christian M. Beusch, Ana Oliveira-Coelho, Kejsi Zeqiraj, Carolin Svensson, Zhongwei Xu, Huqiao Luo, Outi Sareila, Pierre Sabatier, Changrong Ge, Lei Cheng, Vilma Urbonaviciute, Alexander Krämer, Cecilia Lindgren, Sabrina Haag, Johan Viljanen, Roman A. Zubarev, Jan Kihlberg, Anna Linusson, Harald Burkhardt, Rikard Holmdahl
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Åke Wiberg Stiftelse, European Commission, Karolinska Institutet, Knut och Alice Wallenbergs Stiftelse, Novo Nordisk, Vetenskapsrådet, Stiftelsen Lars Hiertas Minne, Stiftelsen Konung Gustaf V:s Jubileumsfond, Reumatikerförbundet, Novo Nordisk Fonden, Ulla och Gustaf af Ugglas Stiftelse, Ministerio de Universidades
OpenAlex ID: W4409744956