title: A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice.
abstract: A combination of genetic and environmental factors can cause autoimmune disease in animals. SKG mice, which are genetically prone to develop autoimmune arthritis, fail to develop the disease under a microbially clean condition, despite active thymic production of arthritogenic autoimmune T cells and their persistence in the periphery. However, in the clean environment, a single intraperitoneal injection of zymosan, a crude fungal beta-glucan, or purified beta-glucans such as curdlan and laminarin can trigger severe chronic arthritis in SKG mice, but only transient arthritis in normal mice. Blockade of Dectin-1, a major beta-glucan receptor, can prevent SKG arthritis triggered by beta-glucans, which strongly activate dendritic cells in vitro in a Dectin-1-dependent but Toll-like receptor-independent manner. Furthermore, antibiotic treatment against fungi can prevent SKG arthritis in an arthritis-prone microbial environment. Multiple injections of polyinosinic-polycytidylic acid double-stranded RNA also elicit mild arthritis in SKG mice. Thus, specific microbes, including fungi and viruses, may evoke autoimmune arthritis such as rheumatoid arthritis by stimulating innate immunity in individuals who harbor potentially arthritogenic autoimmune T cells as a result of genetic anomalies or variations.
authors.affiliation: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshitomi
authors.forename: Noriko
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tagami
authors.forename: Toshiko
authors.initials: T
authors.lastname: Sakihama
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirota
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miki
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005658:Fungi / Q000276:immunology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics / Q000276:immunology; D007274:Injections, Intraperitoneal; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D012330:RNA, Double-Stranded / Q000008:administration & dosage / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors; D014780:Viruses / Q000276:immunology; D047071:beta-Glucans / Q000008:administration & dosage* / Q000276:immunology; D000099181:Dectin-1
chemical_list: D000911:Antibodies, Monoclonal; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D047071:beta-Glucans; D000099181:Dectin-1