epiglucan and Psoriasis

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

Human epidermis plays an important role in host defense by acting as a physical barrier and signaling interface between the environment and the immune system. Pattern recognition receptors (PRRs) are crucial to maintain homeostasis and provide protection during infection, but are also causally involved in monogenic auto-inflammatory diseases. This study aimed to investigate the epidermal expression of PRRs and several associated host defense molecules in healthy human skin, psoriasis, and atopic dermatitis (AD). Using microarray analysis and real-time quantitative PCR, we found that many of these genes are transcribed in normal human epidermis. Only a few genes were differentially induced in psoriasis (CLEC7A (dectin-1), Toll-like receptor (TLR) 4, and mannose receptor C type 1 (MRC1)) or AD (MRC1, IL1RN, and IL1β) compared with normal epidermis. A remarkably high expression of dectin-1 mRNA was observed in psoriatic epidermis and this was corroborated by immunohistochemistry. In cultured primary human keratinocytes, dectin-1 expression was induced by IFN-γ, IFN-α, and Th17 cytokines. Keratinocytes were unresponsive, however, to dectin-1 ligands such as β-glucan or heat-killed Candida albicans, nor did we observe synergy with TLR2/TLR5 ligands. In conclusion, upregulation of dectin-1 in psoriatic lesions seems to be under control of psoriasis-associated cytokines. Its role in the biology of skin inflammation and infection remains to be explored.

Topics: Antigens, Fungal; beta-Glucans; Candida albicans; Cells, Cultured; Dermatitis, Atopic; Epidermal Cells; Epidermis; Gene Expression; Humans; Interferons; Interleukin-17; Interleukin-22; Interleukins; Keratinocytes; Lectins, C-Type; Ligands; Membrane Proteins; Nerve Tissue Proteins; Psoriasis; RNA, Messenger; Up-Regulation