Article Text

PDF
THU0129 Selective elimination of pathogenic TH17 cells from peripheral blood of rheumatoid arthritis patients by a purified fungal polysaccharide
  1. A. Alunno1,
  2. E. Pericolini2,
  3. E. Gabrielli2,
  4. O. Bistoni1,
  5. S. Caterbi1,
  6. E. Bartoloni1,
  7. S.-K. Chow3,
  8. A. Casadevall3,
  9. A. Vecchiarelli2,
  10. R. Gerli1
  1. 1University of Perugia, Rheumatology Unit
  2. 2University of Perugia, Microbiology Section, Perugia, Italy
  3. 3Albert Einstein College of Medicine, Department of Microbiology and Immunology, New York, United States

Abstract

Background It has been shown that the microbial polysaccharide Galactoxylomannan (GalXM) from the opportunistic fungus Cryptococcus neoformans is able to impair T-cell proliferation and to induce apoptosis in T lymphocytes following the interaction with CD45. GalXM administration in experimental arthritis is able to ameliorate synovitis, reduced the concentration of pro-inflammatory cytokines in affected joints and to prevent articular damage.

Objectives Aim of the present study was to investigate the effects of GalXM on circulating T-cell subsets in rheumatoid arthritis (RA) to pursue potential therapeutic application.

Methods Sixty RA patients and 40 HD were included in the study. RA and HD magnetic sorted-CD3+ T cells were cultured in presence or absence of GalXM (10 mg/ml) and activation stimuli (either anti-CD3 antibody of IL-6+TGFβ). Both apoptosis and proliferation assays were performed at different time-points. IL-17 expression and cleaved-caspase 3 were evaluated by flow cytometry, STAT-3 phosphorilation was assessed by western blot.

Results GalXM selectively targeted RA Th17 cells. Indeed, GalXM was able to increase caspase-3 activation and eventually apoptosis rate of this cell subset. Moreover, it was able to reduce STAT3 phosphorilation culminating in reduced IL-17 production. Finally, Th17 cell proliferation was also reduced. In addition, we confirmed that CD45 expression on target T cells is required to mediate GAlXM immune-modulatory effects.

Conclusions This study confirms immune-modulatory effects mediated by GalXM (increase of caspase-3 activation and apoptosis rate, reduction of proliferation, reduction of IL-17 synthesis) in RA Th17 cells. Since Th17 cells represent a pathogenic cell subset deeply involved in the development of rheumatoid synovitis, these findings may suggest possible therapeutic applications of GalXM in RA.

  1. Pericolini E. et al. J Immunol 2009;182:6003

  2. Pericolini E. et al PloS One 2010;5:e12720

Disclosure of Interest None Declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.