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

Masaru Takeshita, Katsuya Suzuki, Yasushi Kondo, Rimpei Morita, Yuumi Okuzono, Keiko Koga, Yoshiaki Kassai, Kanae Gamo, Maiko Takiguchi, Rina Kurisu, Hideyuki Mototani, Yukihiko Ebisuno, Akihiko Yoshimura, Tsutomu Takeuchi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Objectives Rheumatoid arthritis (RA) is an autoimmune disease accompanied by lymphocyte infiltration into joint synovium. While T cells are considered to be important for its pathogenesis, the features that are the most relevant to disease and how they change after treatment remain unclear. The aim of this study was to clarify the characteristics of T cells in RA, comprehensively. Methods We enrolled a total of 311 patients with RA and 73 healthy participants, and carefully classified them by disease state, constructed multiple cohorts and analysed clinical samples from them in a stepwise manner. We performed immunophenotyping with multiple evaluation axes, and two independent transcriptome analyses complementary to each other. Results We identified that â € effector memory-Tfh' subset was specifically expanded in the peripheral blood (PB) of patients with RA in correlation with disease activity, and reverted after treatment. Besides, we revealed distinct features of T cells in synovial fluid (SF) that the expression of Tfh/Tph-related genes and pro-inflammatory cytokines and chemokines, including CXCL13, were significantly enriched, whereas these phenotype were Th1-like. Finally, we identified specific pathways, such as mTORC1, IL-2-stat5, E2F, cell cycle and interferon-related genes, that were significantly enriched in SF, in particular, as well as PB of untreated patients with RA, and notably, these features reverted after treatment. Conclusion Our multi-dimensional investigation identified disease relevant T-cell subsets and gene signatures deeply involved in pathogenesis of RA. These findings could aid in our understanding of essential roles of T cells in RA and will facilitate to development better diagnostic and therapeutic interventions.

Original languageEnglish
Pages (from-to)1346-1356
Number of pages11
JournalAnnals of the rheumatic diseases
Volume78
Issue number10
DOIs
Publication statusPublished - 2019 Oct 1

Keywords

  • T cell
  • rheumatoid arthritis
  • synovial fluid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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