Variants of beta-glucan polysaccharides downregulate autoimmune inflammation

Area of Science:

• Immunology
• Microbiology
• Rheumatology

Background:

• Infections involving polysaccharides from bacteria and yeasts can trigger inflammatory conditions like psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA).
• Beta-glucans are polysaccharides with immunomodulatory properties that warrant investigation in autoimmune disease models.

Purpose of the Study:

• To investigate the therapeutic effects of different beta-glucan variants (1,6-β-glucan, 1,3-β-glucan, and 1,3-1,6-β-glucan) on established arthritis and psoriasis/PsA-like symptoms in susceptible mouse models.
• To determine the role of the macrophage mannose receptor (MMR/CD206) in beta-glucan-mediated immune regulation.

Main Methods:

• Utilized collagen antibody-induced arthritis and mannan-induced psoriasis (MIP) models in Ncf1-mutated B10.Q mice, which are highly susceptible to autoimmune diseases.
• Administered three common beta-glucan variants to mice before, during, or after induction of disease models.
• Assessed disease severity, macrophage populations (resident and infiltrating), and MMR/CD206 dependency.

Main Results:

• Beta-glucans significantly down-regulated disease progression in arthritis and PsA-like models, regardless of administration timing relative to mannan exposure.
• The protective effects were dependent on the macrophage mannose receptor (MMR/CD206), with long-term protection exceeding short-term benefits.
• Beta-glucans did not induce arthritis or psoriasis in wild-type mice but ameliorated PsA-like symptoms in susceptible mice, with observed changes in peritoneal macrophage populations.

Conclusions:

• Beta-glucans demonstrate significant potential in ameliorating PsA-like symptoms and regulating inflammatory arthritis, mediated through MMR/CD206-dependent macrophage modulation.
• These findings suggest beta-glucans as a novel therapeutic avenue for managing inflammatory conditions such as psoriasis and psoriatic arthritis.