title: A microbial polysaccharide reduces the severity of rheumatoid arthritis by influencing Th17 differentiation and proinflammatory cytokines production.
abstract: Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease characterized by chronic joint inflammation with subsequent cartilage and bone destruction. RA is emerging as a model of IL-17-driven autoimmune inflammatory disease. IL-17 is a marker for Th17 cells, with its master regulator being the retinoic acid receptor-related orphan receptor (RORgammat) regulated by STAT3 signaling. Glucuronoxylomannan (GXM), a polysaccharide representing the main component of the capsular material of the opportunistic yeast Cryptococcus neoformans, exhibits potent immunosuppressive properties both in vitro and in vivo. The present study investigates the effects of GXM treatment on the progression of collagen-induced arthritis. GXM suppressed clinical signs of collagen-induced arthritis and blocked joint erosion progression. This effect was mediated by down-regulation of key cytokines involved in the pathogenesis of RA such as TNF-alpha and IL-1beta, and up-regulation of the inhibitory cytokine IL-10. Moreover, a reduction of IL-6 and TGF-beta, which inhibit Th17 differentiation with consequent decreased IL-17 production at the local and systemic level, was observed. The effect of GXM on Th17 differentiation mirrored the reduction in STAT3 activation and inhibition of RORgammat synthesis. Consequently, this work highlights the beneficial properties of an efficacious compound that could eventually be destined to the clinic.
authors: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
authors: Claudia
authors: C
authors: Monari
authors: Sara
authors: S
authors: Bevilacqua
authors: Miranda
authors: M
authors: Piccioni
authors: Eva
authors: E
authors: Pericolini
authors: Stefano
authors: S
authors: Perito
authors: Mario
authors: M
authors: Calvitti
authors: Francesco
authors: F
authors: Bistoni
authors: Thomas R
authors: TR
authors: Kozel
authors: Anna
authors: A
authors: Vecchiarelli
mesh_terms: D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000276:immunology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001862:Bone Resorption / Q000276:immunology / Q000473:pathology; D024043:Collagen Type II / Q000633:toxicity; D003455:Cryptococcus neoformans / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000276:immunology; D015994:Incidence; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000276:immunology / Q000473:pathology; D011134:Polysaccharides / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000946:Antigens, Fungal; D024043:Collagen Type II; D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D020381:Interleukin-17; D011134:Polysaccharides; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C027478:glucuronoxylomannan