Abstract
The persistence of activated T cells in rheumatoid arthritis (RA) synovium may be attributable to increased homing, increased retention or a possible imbalance between cell proliferation and programmed cell death. Induction of apoptosis may represent a potential therapeutic approach. Galactoxylomannan (GalXM) from the opportunistic fungus Cryptococcus neoformans can interact with T cells and induce T-cell apoptosis through the inhibition of CD45 phosphatase activity. The aim of this study was to determine the effect of GalXM on circulating T cells from patients with RA and the underlying mechanisms. GalXM immunomodulating effect on apoptosis and signal transduction pathway involved in IL-17A production was evaluated on T cells. RA T-cell apoptosis, higher than that of control T cells, was further increased by GalXM through induction of caspase-3 activation. Activated T cells expressing the CD45RO molecule and producing IL-17A were the main target of GalXM-induced apoptosis. GalXM induced consistent impairment of IL-17A production and inhibition of STAT3, which was hyperactivated in RA. In conclusion, GalXM triggered apoptosis of activated memory T cells and interfered with IL-17A production in RA. These data suggest therapeutic targeting of deleterious Th17 cells in RA and other autoimmune diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Apoptosis / drug effects
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Apoptosis / immunology
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / pathology
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Caspase 3 / genetics
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Caspase 3 / immunology
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Cell Proliferation / drug effects
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Cells, Cultured
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Cryptococcus neoformans / chemistry
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Female
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Fungal Polysaccharides / isolation & purification
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Fungal Polysaccharides / pharmacology*
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Gene Expression / drug effects
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Humans
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Immunologic Memory
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Interleukin-17 / antagonists & inhibitors*
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Interleukin-17 / biosynthesis
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Interleukin-17 / immunology
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Leukocyte Common Antigens / antagonists & inhibitors*
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Leukocyte Common Antigens / genetics
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Leukocyte Common Antigens / immunology
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Lymphocyte Activation
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Male
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Middle Aged
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Polysaccharides / isolation & purification
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Polysaccharides / pharmacology*
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STAT3 Transcription Factor / antagonists & inhibitors
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / immunology
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Signal Transduction / drug effects
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Synovial Fluid / cytology
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Synovial Fluid / drug effects
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Th17 Cells / drug effects*
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Th17 Cells / immunology
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Th17 Cells / pathology
Substances
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Fungal Polysaccharides
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IL17A protein, human
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Interleukin-17
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Polysaccharides
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STAT3 Transcription Factor
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STAT3 protein, human
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galactoxylomannan
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Leukocyte Common Antigens
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PTPRC protein, human
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Caspase 3