A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice.
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.
Yoshitomi
Hiroyuki
H
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Sakaguchi
Noriko
N
Kobayashi
Katsuya
K
Brown
Gordon D
GD
Tagami
Tomoyuki
T
Sakihama
Toshiko
T
Hirota
Keiji
K
Tanaka
Satoshi
S
Nomura
Takashi
T
Miki
Ichiro
I
Gordon
Siamon
S
Akira
Shizuo
S
Nakamura
Takashi
T
Sakaguchi
Shimon
S
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
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