Study of dietary‑induced progression of psoriasis‑like mice based on gut macrophage polarization.

The aim of the present study was to investigate the influence of stimulating food (SF), a Traditional Chinese Medicine term for a high protein, high fat diet, on psoriasis exacerbation. It was hypothesized that SF disposed psoriasis-like aggravation might be related to inflammatory pathways induction via gut dysbiosis. In the present study, mice were fed either an SF or normal diet for 4 weeks. In the last week, their back hair was removed to establish psoriasis-like dermatitis by imiquimod. After sacrifice, blood samples, alimentary tissues and skin lesions were collected and tested by enzyme-linked immunosorbent assay, western blotting, immunohistochemistry and immunofluorescence. Compared with normal diet groups, body weight and blood glucose of SF diet mice were not increased, but they exhibited higher modified Psoriasis Area and Severity Index scores and corresponding epithelial hyperproliferation. Unexpectedly, skin lesions showed abnormal lower protein expressions of Notch and TLR-2/NF-κB p65 signaling pathway, which was attributable to severe skin damage. No difference was observed in the structure and inflammatory cell infiltration of the gut between groups. Instead, macrophage polarization (M1/M2) in the gut of the SF diet group marked by high expression of CD11b (a marker of macrophage, M1) and mild low expression of MRC1 (a marker of macrophage, M2), which resulted in increased TNF-α, decreased IL-10, IL-35, and unchanged IL-17 in serum. Furthermore, serum derived from SF diet mice promoted translocation of NF-κB p65 in HaCaT cells, which indirectly suggested a systemic inflammation. These results suggested that mice fed a continuous SF diet for a time could change gut macrophage polarization, which secretes proinflammatory cytokines into blood circulation. Once transported to skin lesions, these cytokines activate psoriasis tissue resident immune cells and present as psoriasis exacerbation.