epiglucan and Arthritis

Common infections and polysaccharides, from bacteria and yeasts, could trigger psoriasis and psoriatic arthritis (PsA), and possibly rheumatoid arthritis (RA). The objective of this study was to investigate the effects of β-glucan polysaccharides in the effector phase of arthritis and as regulators of psoriasis and PsA-like symptoms in mice. Collagen antibody induced arthritis was studied as a model of RA and mannan-induced psoriasis (MIP) was used as model for psoriasis and PsA, using mice with a mutation of Ncf1 on the B10.Q genetic background, making them highly disease susceptible. The mice were exposed to three common variants: 1,6-β-glucan, 1,3-β-glucan and 1,3-1,6-β-glucan. These β-glucans down-regulated disease in mice if administered simultaneously, before or after mannan. Interestingly, the protection was macrophage mannose receptor (MMR/CD206) dependent with a more pronounced protection long-term than short-term. The number of resident peritoneal macrophages decreased after in vivo challenge with β-glucan and mannan compared to mannan alone, whereas the numbers of infiltrating cells correspondingly increased, further indicating macrophages as key for β-glucan mediated regulation. At the doses tested, β-glucans could not induce arthritis, psoriasis or PsA in wild-type mice. However, β-glucans could ameliorate the PsA-like symptoms representing a new unforeseen possibility to explore for future clinical treatment.

Topics: Animals; Arthritis; beta-Glucans; Glucans; Humans; Inflammation; Male; Mannans; Mice; Polysaccharides; Prostate-Specific Antigen; Psoriasis

Arthritis in a genetically susceptible SKG strain of mice models a theoretical paradigm wherein autoimmune arthritis arises because of interplay between preexisting autoreactive T cells and environmental stimuli. SKG mice have a point mutation in ZAP-70 that results in attenuated TCR signaling, altered thymic selection, and spontaneous production of autoreactive T cells that cause arthritis following exposure to microbial β-glucans. In this study, we identify Nod2, an innate immune receptor, as a critical suppressor of arthritis in SKG mice. SKG mice deficient in Nod2 (Nod2

Topics: Animals; Arthritis; Autoimmune Diseases; beta-Glucans; Cells, Cultured; Cytokines; Disease Models, Animal; Humans; Immune Tolerance; Immunity, Innate; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Mutant Strains; Mutation; Nod2 Signaling Adaptor Protein; Th17 Cells; ZAP-70 Protein-Tyrosine Kinase

Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells.. We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice--a recently described animal model of RA--by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction.. Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.

Topics: Animals; Antibodies; Arthritis; Autoimmunity; beta-Glucans; CD4 Antigens; Cell Polarity; Chronic Disease; Disease Progression; Forkhead Transcription Factors; Gene Expression Regulation; Immunization; Immunocompetence; Interleukin-17; Lymph Nodes; Mice; Synovial Membrane; T-Lymphocytes, Regulatory; Time Factors

SKG mice are a recently established experimental model for rheumatoid arthritis (RA). Although they spontaneously develop chronic autoimmune arthritis under conventional conditions, SKG mice failed to develop chronic arthritis in a strictly controlled specific pathogen-free (SPF) environment. Beta-glucan (BG) from Laminaria digitata, laminarin (LAM), induced arthritis under SPF conditions, thus BG would be a pathogenic factor for arthritis in SKG mice. Therefore, we prepared BG from Candida albicans, a pathogenic fungus and investigated whether BG from C. albicans induced arthritis in SKG mice under SPF conditions. SKG mice were injected intraperitoneally with particulate BG (oxidative-Candida albicans (OX-CA)), soluble BG (Candida soluble beta-glucan (CSBG)) from C. albicans and LAM as a positive control. In addition, schizophyllan (SPG) from Schizophyllum commune or Mycobacterium whole cells were injected into SKG mice to induce arthritis. Mice injected with OX-CA, CSBG and SPG had more severe arthritis than with LAM, and whole Mycobacterium cells. IL-6 concentration in sera from SKG mice injected with OX-CA or CSBG was high, whereas not detected in sera from mice treated with LAM. In histological analysis, infiltration of inflammatory cells was observed in SKG mice injected with BG. These results suggest that fungal infection may be a factor to induce and exacerbate autoimmune diseases such as RA.

Topics: Adjuvants, Immunologic; Animals; Arthritis; Autoimmune Diseases; beta-Glucans; Candida albicans; Cell Wall; Female; Interleukin-6; Male; Mice; Mice, Inbred Strains; Mycobacterium tuberculosis; Sizofiran