title: The microbial capsular polysaccharide galactoxylomannan inhibits IL-17A production in circulating T cells from rheumatoid arthritis patients.
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.
authors: Microbiology Section, Department of Experimental Medicine and Biochemical Science, University of Perugia, Perugia, Italy.
authors: Eva
authors: E
authors: Pericolini
authors: Alessia
authors: A
authors: Alunno
authors: Elena
authors: E
authors: Gabrielli
authors: Elena
authors: E
authors: Bartoloni
authors: Elio
authors: E
authors: Cenci
authors: Siu-Kei
authors: SK
authors: Chow
authors: Giovanni
authors: G
authors: Bistoni
authors: Arturo
authors: A
authors: Casadevall
authors: Roberto
authors: R
authors: Gerli
authors: Anna
authors: A
authors: Vecchiarelli
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003455:Cryptococcus neoformans / Q000737:chemistry; D005260:Female; D062610:Fungal Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D062610:Fungal Polysaccharides; C508717:IL17A protein, human; D020381:Interleukin-17; D011134:Polysaccharides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C043689:galactoxylomannan; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D053148:Caspase 3