A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice.
A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice.
复制标题
DOI：
10.1084/jem.20041758
复制
发表时间：
2005-03-21
期刊：
影响因子：
--
通讯作者：
Sakaguchi S
中科院分区：
文献类型：
--
作者：
Yoshitomi H;Sakaguchi N;Kobayashi K;Brown GD;Tagami T;Sakihama T;Hirota K;Tanaka S;Nomura T;Miki I;Gordon S;Akira S;Nakamura T;Sakaguchi S
遗传和环境因素的结合可导致动物的自身免疫性疾病。SKG小鼠在遗传上易于发展自身免疫性关节炎，在微生物清洁的条件下不能发展这种疾病，尽管致关节炎自身免疫T细胞的胸腺活性产生及其在外周的持久性。然而，在清洁的环境中，单次腹膜内注射酵母聚糖（一种粗制真菌β-葡聚糖）或纯化的β-葡聚糖（如凝胶多糖和海带多糖）可在SKG小鼠中引发严重的慢性关节炎，但在正常小鼠中仅引发一过性关节炎。阻断Dectin-1（一种主要的β-葡聚糖受体）可以预防β-葡聚糖引发的SKG关节炎，β-葡聚糖在体外以Dectin-1依赖性但Toll样受体非依赖性的方式强烈激活树突状细胞。此外，针对真菌的抗生素治疗可以在关节炎易感的微生物环境中预防SKG关节炎。多次注射聚肌胞-聚胞苷酸双链RNA也会在SKG小鼠中引发轻度关节炎。因此，特定的微生物，包括真菌和病毒，可能会引起自身免疫性关节炎，如类风湿性关节炎，刺激先天免疫的个体谁窝藏潜在的致关节炎性自身免疫T细胞作为遗传异常或变异的结果。
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 β-glucan, or purified β-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 β-glucan receptor, can prevent SKG arthritis triggered by β-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.
登录
查看更多内容
影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
Dectin-1介导β-葡聚糖的生物学作用。
DOI：
10.1084/jem.20021890
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brown GD;Herre J;Williams DL;Willment JA;Marshall AS;Gordon S
通讯作者：
Gordon S
影响因子：
82.9
作者：
Millar, DG;Garza, KM;Ohashi, PS
通讯作者：
Ohashi, PS
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
11.4
作者：
KEFFER, J;PROBERT, L;KOLLIAS, G
通讯作者：
KOLLIAS, G