A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice -- Yoshitomi et al. 201 (6): 949 -- The Journal of Experimental Medicine

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A role for fungal ß-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 ß-glucan, or purified ß-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

ß-glucan receptor, can prevent SKG arthritis triggered by ß-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.

Abbreviations used: CP, cyclophosphamide; ITS1, internal transcriber

spacer 1; poly(I:C), polyinosinic-polycytidylic acid; PTX, pertussis

toxin; RA, rheumatoid arthritis; SPF, specific pathogen-free; TLR,

Toll-like receptor.

H. Yoshitomi and N. Sakaguchi contributed equally to this work.

T. Tagami's present address is Ajinomoto Co., Inc., Kawasaki 210-8681,

Japan.

T. Sakihama's present address is Laboratory for Systems Biology and

Medicine, Research Center for Advanced Science and Technology,

University of Tokyo, Tokyo 153-8904, Japan.

http://www.jem.org/cgi/content/abstract/201/6/949

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