A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice

• DOI: 10.1084/jem.20041758
• Publication Date: 2005-03-21T19:32:53Z
• Authors: Hiroyuki Yoshitomi; Noriko Sakaguchi; Katsuya Kobayashi; Gordon D. Brown; Tomoyuki Tagami; Toshiko Sakihama; Keiji Hirota; Satoshi Tanaka; Takashi Nomura; Ichiro Miki; Siamon Gordon; Shizuo Akira; Takashi Nakamura; Shimon Sakaguchi
• Keywords: Mice, Knockout; 0301 basic medicine; Mice, Inbred BALB C; Membrane Glycoproteins; T-Lymphocytes; Toll-Like Receptors; Fungi; Antibodies, Monoclonal; Genetic Variation; Membrane Proteins; Nerve Tissue Proteins; Receptors, Cell Surface; Dendritic Cells; Arthritis, Experimental; Article; 3. Good health; Arthritis, Rheumatoid; Mice; 03 medical and health sciences; Animals; Genetic Predisposition to Disease; Lectins, C-Type; Injections, Intraperitoneal; RNA, Double-Stranded

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.