Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell.

Area of Science:

• Immunology
• Rheumatology
• Molecular Biology

Background:

• Rheumatoid arthritis (RA) is an autoimmune disease characterized by lymphocyte infiltration in the synovium.
• The precise role and evolving characteristics of T cells in RA pathogenesis and treatment response remain incompletely understood.

Purpose of the Study:

• To comprehensively characterize T cell subsets and their molecular features in rheumatoid arthritis.
• To identify T cell-related biomarkers associated with disease activity and treatment outcomes in RA.

Main Methods:

• Multi-dimensional immunophenotyping and two complementary transcriptome analyses were performed.
• Analysis included clinical samples from 311 RA patients and 73 healthy controls, classified by disease state.
• Stratified analysis was conducted across multiple cohorts and sample types (peripheral blood and synovial fluid).

Main Results:

• An expansion of 'effector memory-Tfh' T cells in peripheral blood correlated with RA disease activity and normalized post-treatment.
• Synovial fluid T cells showed enrichment of Tfh/Tph-related genes, pro-inflammatory cytokines (e.g., CXCL13), and a Th1-like phenotype.
• Specific pathways (mTORC1, IL-2-stat5, E2F, cell cycle, interferon) were enriched in RA patients' samples and reverted after treatment.

Conclusions:

• Multi-dimensional analysis revealed disease-relevant T cell subsets and gene signatures crucial to RA pathogenesis.
• These findings enhance understanding of T cell functions in RA and may guide the development of novel diagnostic and therapeutic strategies.