Quantitative and qualitative characterization of expanded CD4 + T cell clones in rheumatoid arthritis patients

Kazuyoshi Ishigaki, Hirofumi Shoda, Yuta Kochi, Tetsuro Yasui, Yuho Kadono, Sakae Tanaka, Keishi Fujio, Kazuhiko Yamamoto

研究成果: Article査読

37 被引用数 (Scopus)

抄録

Rheumatoid arthritis (RA) is an autoimmune destructive arthritis associated with CD4 + T cell-mediated immunity. Although expanded CD4 + T cell clones (ECs) has already been confirmed, the detailed characteristics of ECs have not been elucidated in RA. Using combination of a single-cell analysis and next-generation sequencing (NGS) in TCR repertoire analysis, we here revealed the detailed nature of ECs by examining peripheral blood (PB) from 5 RA patients and synovium from 1 RA patient. When we intensively investigated the single-cell transcriptome of the most expanded clones in memory CD4 + T cells (memory-mECs) in RA-PB, senescence-related transcripts were up-regulated, indicating circulating ECs were constantly stimulated. Tracking of the transcriptome shift within the same memory-mECs between PB and the synovium revealed the augmentations in senescence-related gene expression and the up-regulation of synovium-homing chemokine receptors in the synovium. Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs. Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes. Our approach may provide new insights into the pathophysiology of RA.

本文言語English
論文番号12937
ジャーナルScientific reports
5
DOI
出版ステータスPublished - 2015 8月 6
外部発表はい

ASJC Scopus subject areas

  • 一般

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