To comprehensively characterize early CD4+ and CD8+ T cell responses to homocitrullinated peptides (HomoCitP) in a humanized mouse model of rheumatoid arthritis (RA).
Approach:
Mouse Model: Utilized humanized SE-expressing HLA-DRB1*04 transgenic (DR4tg) mice to study immune responses to HomoCitP.
Immunization: Mice were immunized with HomoCitJED peptide containing homocitrulline and a control peptide, LysJED.
Cell Analysis: Spleens and draining lymph nodes were harvested for single-cell suspensions and analyzed using flow cytometry.
Cytokine Detection: Proliferation and cytokine production were assessed in splenocytes and draining lymph node cells.
Key Findings:
CD4+ T cells from DR4tg mice proliferated in response to HomoCitP.
Increased production of pro-inflammatory cytokines was observed in response to HomoCitP.
Interpretation:
Homocitrullinated peptides can induce pro-inflammatory T cell activation.
Limitations:
The study focused on a specific mouse model and may not fully represent human RA.
Potential differences in immune responses between mice and humans were not addressed.
Conclusion:
This study provides insights into the cellular mechanisms through which homocitrullinated peptides may contribute to RA pathogenesis.
Joint tenderness showed broader associations with concurrent ultrasound abnormalities than patient-reported pain among anti-cyclic citrullinated peptide–positive patients without clinical arthritis.
Analysis of East Asian genetic data found a modest inverse association between rheumatoid arthritis susceptibility and periodontitis risk, though researchers said the findings require confirmation in independent cohorts.
