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- W4318393771 abstract "In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach of tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable of non-endogenous C-terminal citrullination with potential to generate citrullinated autoantigens. Here we document how C-terminal citrullination of ovalbumin peptide323-339 alters the interaction between antigen-presenting cells and OTII T cells to induce functional changes in responding T cells. These data reveal that C-terminal citrullination is sufficient to breach T cell peripheral tolerance in vivo and reveal the potential of C-terminal citrullination to lower the threshold for T cell activation. Finally, we demonstrate a role for the IL-2/STAT5/CD25 signalling axis in breach of tolerance. Together, our data identify a tractable mechanism and targetable pathways underpinning breach of tolerance in rheumatoid arthritis and provide new conceptual insight into the origins of anti-citrullinated autoimmunity." @default.
- W4318393771 created "2023-01-29" @default.
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- W4318393771 date "2023-02-01" @default.
- W4318393771 modified "2023-10-01" @default.
- W4318393771 title "C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance" @default.
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- W4318393771 doi "https://doi.org/10.1016/j.jaut.2023.102994" @default.
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