Itaconate reduces proliferation and migration of fibroblast-like synoviocytes and ameliorates arthritis models

Maria Tada, Yuki Kudo, Michihito Kono*, Masatoshi Kanda, Shuhei Takeyama, Kodai Sakiyama, Hotaka Ishizu, Tomohiro Shimizu, Tsutomu Endo, Ryo Hisada, Yuichiro Fujieda, Masaru Kato, Olga Amengual, Norimasa Iwasaki, Tatsuya Atsumi

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

8 被引用数 (Scopus)

抄録

Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.

本文言語英語
論文番号110255
ジャーナルClinical Immunology
264
DOI
出版ステータス出版済み - 2024/07

ASJC Scopus 主題領域

  • 免疫アレルギー学
  • 免疫学

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