A role for fungal β-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 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.

Inhibition of cytokine response to TLR stimulation and alleviation of collagen‐induced arthritis in mice by Schistosoma japonicum peptide SJMHE1

“…However, this peptide induced protection against CIA whether or not it interfered with the differentiation and function of DC and/or macrophage requires further analysis as previously described 11. Maturation and activation of DC and/or macrophages are key steps in triggering the priming of auto‐reactive peripheral T cells, which then drive the development of inflammatory responses in arthritis 52; whereas tolerogenic DC and macrophages are known to induce tolerance by Tregs in various autoimmune diseases, including CIA 53. Thus, considerable work is still needed to define the mechanisms of immune alteration and determine whether therapies for allergies or autoimmunities could be developed from this peptide.…”

Gamma/delta T cells are the predominant source of interleukin‐17 in affected joints in collagen‐induced arthritis, but not in rheumatoid arthritis

“…Eight-week-old male mice were used for induction of CIA, and 2-week-old mice were used to analyze thymocytes. The procedures for the induction of arthritis in SKG mice were described previously (17). Mice were maintained in our animal facility under specific pathogen-free conditions, and all animal procedures were approved by the Ethics Committee of Kyoto University.…”

“…To elucidate the pathologic differences from other arthritis models, the same analysis was performed using SKG mice (21). SKG mice carry a point mutation of the SKG is a BALB/c background strain, and autoimmune arthritis in SKG mice is induced using zymosan as an adjuvant (17,21). To exclude the possibility that IL-17-producing ␥/␦ T cells are absent in the joints of SKG mice with arthritis because of the differences in strain and adjuvant compared with CIA, the absolute numbers of cell subsets from the joints of SKG or BALB/c mice immunized with CFA plus type II collagen were counted.…”

Autoimmune priming, tissue attack and chronic inflammation — The three stages of rheumatoid arthritis

“…This is also the triggering event in animal models, such as adjuvant-induced arthritis (e.g. PIA) [30], maybe the intestinal dependent spontaneous arthritis in the glucoss-6-phospho-isomerase TCR transgenic mouse (the KxBN mouse) [37] or the adjuvant (betaglucan) dependent arthritis in the mouse strain with a mutation in the ZAP70 gene (the SKG mouse model) [38]. However, the exact parallel with human RA, or subtypes of human RA, regarding the proper combination of environmental factor (i.e.…”