Abstract
Psoriasis is a common, chronic inflammatory skin disease characterized by epidermal hyperplasia via the IL-23/IL-17 axis. Various studies have indicated the association between obesity and psoriasis, however, the underlying mechanisms remains unclarified. To this end, we focused on high-fat diet (HFD) in this study, because HFD is suggested as a contributor to obesity, and HFD-fed mice exhibit exacerbated psoriatic dermatitis. Using murine imiquimod (IMQ)-induced psoriasis and HFD-induced obesity models, we have revealed a novel mechanism of HFD-induced exacerbation of psoriatic dermatitis. HFD-fed mice exhibited aggravated psoriatic dermatitis, which was accompanied with increased accumulation of IL-17A-producing Vγ4+ γδ T cells in the skin. HFD also induced the increase of Vγ4+ γδ T cells in other organs such as skin draining lymph nodes, which preceded the increase of them in the skin. In addition, HFD-fed mice displayed increased expression of several γδ T cell-recruiting chemokines in the skin. On the other hand, ob/ob mice, another model of murine obesity on normal diet, did not exhibit aggravated psoriatic dermatitis nor accumulation of γδ T cells in the dermis. These results indicate that HFD is a key element in exacerbation of IMQ-induced psoriatic dermatitis, and further raise the possibility of HFD as a factor that links obesity and psoriasis.
Highlights
The prevalence of obesity in developed countries has approximately doubled over the last two decades[1]
Recent studies suggest that high-fat diet (HFD), which potentially induces obesity, is responsible for the exacerbation of psoriatic dermatitis[13,27], which is in line with our current findings
We consider that the high expression of IL-17A in the skin of HFD-fed mice in basal condition is the key point in the exacerbated IMQ-induced psoriatic dermatitis in HFD-fed mice, because IL-17A can significantly enhance the functions of various proinflammatory cytokines
Summary
The prevalence of obesity in developed countries has approximately doubled over the last two decades[1]. To examine a novel mechanism by which HFD promotes the development of psoriasis, we first confirmed the HFDinduced exacerbation of psoriatic dermatitis using a HFD-fed obese mice and an imiquimod (IMQ)-induced psoriasis model[17].
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