Aberrant overexpression of the autoantigen protein vimentin promotes Th17 cell differentiation and autoimmune arthritis via activation of STAT3 signaling

Clin Immunol. 2024 Dec:269:110383. doi: 10.1016/j.clim.2024.110383. Epub 2024 Oct 23.

Abstract

Vimentin contributes to the positioning and function of organelles, cell migration, adhesion, and division. However, secreted vimentin accumulates on the cell surface (Mor-Vaknin et al., 2003; Ramos et al., 2020 [1,2]) where it acts as a coreceptor for viral infection and as an autoantigen in inflammatory and autoimmune diseases. The roles of vimentin in Th17 cells were examined in mice with knockdown of vimentin. We also examined whether STAT3 is required for vimentin expression. Vimentin expression was significantly increased in Th17 cells through STAT3 activation, and vimentin+ IL-17+ T cells were markedly increased in the joint and spleen tissues of CIA mice. The arthritis score and expression levels of proinflammatory cytokines were significantly decreased in CIA mice treated with vimentin shRNA vector. In this study, we demonstrated that vimentin is significantly expressed in Th17 cells through STAT3 activation. Our results provide new insights into the role of vimentin in Th17 cells and the complex pathogenesis of RA.

Keywords: Rheumatoid arthritis; STAT3; Th17; Vimentin; ZPB89.

MeSH terms

  • Animals
  • Arthritis, Experimental* / genetics
  • Arthritis, Experimental* / immunology
  • Arthritis, Experimental* / metabolism
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Autoantigens* / immunology
  • Cell Differentiation* / immunology
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Male
  • Mice
  • Mice, Inbred DBA
  • STAT3 Transcription Factor* / genetics
  • STAT3 Transcription Factor* / immunology
  • STAT3 Transcription Factor* / metabolism
  • Signal Transduction* / immunology
  • Th17 Cells* / immunology
  • Vimentin* / genetics
  • Vimentin* / immunology
  • Vimentin* / metabolism

Substances

  • Vimentin
  • STAT3 Transcription Factor
  • Autoantigens
  • Stat3 protein, mouse
  • Interleukin-17