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Updated: Jan 7, 2026

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(5R)-5-hydroxytriptolide inhibits proliferation, invasion, and migration of rheumatoid arthritis fibroblast-like

Lingxia Xu1, Cen Chang2, Xinpeng Zhou3

  • 1Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200052, China; Rheumatology Department, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian Province 361009, China.

International Immunopharmacology
|January 4, 2026
PubMed
Abstract

Insights

(5R)-5-Hydroxytriptolide (T8) targets CD74 to inhibit rheumatoid arthritis fibroblast-like synoviocytes. This study reveals T8

Area of Science:

  • Rheumatology
  • Molecular Biology
  • Proteomics

Background:

  • Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) drive disease pathogenesis.
  • (5R)-5-Hydroxytriptolide (LLDT-8, T8) inhibits RA-FLS but its molecular targets are unknown.

Purpose of the Study:

  • To identify the molecular targets of T8 in RA-FLS.
  • To elucidate the mechanism by which T8 modulates RA-FLS function.

Main Methods:

  • Integrated 4D-DIA quantitative proteomics and single-cell transcriptomics.
  • Functional validation including pharmacological inhibition, transwell migration, western blot, and qRT-PCR.
  • Multi-omics correlation analysis to identify key regulatory pathways.

Main Results:

  • CD74 was identified as aberrantly overexpressed in RA-FLS and is a direct target of T8.
  • T8 treatment suppressed CD74 expression, RA-FLS proliferation, invasion, migration, and cytokine production.
  • T8 disrupted the JNK-c-Jun signaling cascade by modulating CD74, establishing a CD74-JNK-c-Jun regulatory axis.

Conclusions:

  • CD74 is a critical downstream target of T8 in RA-FLS.
  • T8 exerts its therapeutic effects by modulating the CD74-JNK-c-Jun axis.
  • T8 demonstrates novel therapeutic potential for rheumatoid arthritis treatment.
Keywords:
(5R)-5-HydroxytriptolideCD74Fibroblast-like synoviocytesRheumatoid arthritis

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