An innovative immunotherapeutic strategy for rheumatoid arthritis: Selectively suppressing angiogenesis and osteoclast differentiation by fully human antibody targeting thymocyte antigen-1

Exp Cell Res. 2023 Mar 1;424(1):113490. doi: 10.1016/j.yexcr.2023.113490. Epub 2023 Jan 24.

Abstract

Thymocyte antigen-1 (THY-1)is a potential target for rheumatoid arthritis (RA) treatment, and THY-1 positive fibroblast-like synoviocytes (FLS) are enriched in the synovium of RA patients and participate in angiogenesis to accelerate RA progression. In this study, we screened an antibody targeting THY-1 (THY-1 Ab) and explored its mechanism in alleviating RA progression. THY-1 Ab was screened from ScFv phage antibody library by phage display technology (PDT). THY-1 Ab-treated collagen induced arthritis (CIA) mice had lower degree of arthritis scores. We explore the mechanism of THY-1 Ab in alleviating RA progression. THY-1 Ab can remarkably inhibit the secretion of pro-inflammatory factors and promote the secretion of anti-inflammatory factors. Further experiments showed that THY1 Ab downregulated the expression of JUNB by the hsa_circ_0094342/miRNA-155-5P/SPI1 axis, inhibited RA angiogenesis and osteoclast differentiation, and relieved RA progression. These findings support that THY-1 Ab is a promising therapeutic antibody for RA treatment.

Keywords: Angiogenesis; Osteoclast differentiation; Phage display technology; Rheumatoid arthritis; THY-1 Ab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • Arthritis, Experimental* / metabolism
  • Arthritis, Experimental* / therapy
  • Arthritis, Rheumatoid* / metabolism
  • Arthritis, Rheumatoid* / therapy
  • Cell Proliferation
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Humans
  • Immunotherapy
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteoclasts / metabolism
  • Synovial Membrane / metabolism
  • Thymocytes / metabolism

Substances

  • MicroRNAs
  • MIRN155 microRNA, human
  • Mirn155 microRNA, mouse
  • Antigens