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.
Pericolini E. et al. J Immunol 2009;182:6003
Pericolini E. et al PloS One 2010;5:e12720
Disclosure of Interest None Declared
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