Department of Dermatology Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
Singapore Immunology Network (SIgN) and Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, IMMUNOS Building, Biopolis, 138648, Singapore.
Sci Rep. 2017 Oct 26;7(1):14076. doi: 10.1038/s41598-017-14292-1.
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.
银屑病是一种常见的慢性炎症性皮肤病,其特征是通过 IL-23/IL-17 轴导致表皮过度增生。多项研究表明肥胖与银屑病之间存在关联,但潜在机制尚不清楚。为此,我们在这项研究中专注于高脂肪饮食(HFD),因为 HFD 被认为是肥胖的一个促成因素,并且 HFD 喂养的小鼠表现出银屑病样皮炎加重。通过使用鼠咪喹莫特(IMQ)诱导的银屑病和 HFD 诱导的肥胖模型,我们揭示了 HFD 诱导银屑病样皮炎加重的新机制。HFD 喂养的小鼠表现出加重的银屑病样皮炎,这伴随着皮肤中产生 IL-17A 的 Vγ4 γδ T 细胞的积累增加。HFD 还诱导其他器官(如皮肤引流淋巴结)中 Vγ4 γδ T 细胞的增加,这先于皮肤中它们的增加。此外,HFD 喂养的小鼠皮肤中几种招募 γδ T 细胞的趋化因子的表达增加。另一方面,ob/ob 小鼠,另一种在正常饮食下的肥胖小鼠模型,并没有表现出加重的银屑病样皮炎或真皮中 γδ T 细胞的积累。这些结果表明 HFD 是加重 IMQ 诱导的银屑病样皮炎的关键因素,并进一步提示 HFD 可能是肥胖和银屑病之间的关联因素。