Certain dietary components are implicated in the exacerbation of psoriasis symptoms, according to study data published in the Journal of Investigative Dermatology. Wild-type mice fed a Western diet (WD), characterized by high simple sugar and fat intake, developed psoriasiform dermatitis (PsD) before significant weight gain occurred, suggesting that diet alone, rather than obesity, precipitates psoriatic inflammation.

Laboratory mice were fed a WD or a nutritionally matched control diet and observed for up to 3 months. Ear thickness, used as a proxy for skin inflammation, was continuously measured throughout the study period. Histological analyses were conducted on ear and paw skin samples; epidermal hyperplasia and transepidermal marker loss were compared in diet groups. Real-time polymerase chain reaction was used to assess expression of proinflammatory markers in skin samples, including Th17 cytokines and gamma-delta (γδ) T cells. As prior research has suggested that long-term WD intake may cause dysregulated bile acid signaling, bile acid sequestrant cholestyramine (CSM) was administered to a subset of mice receiving WD. CSM-supplemented mice were compared with WD-fed mice not receiving CSM.

In 4 weeks, WD-fed mice displayed clinically visible erythema and scaling of the ears, neither of which was present in control mice. Greater epidermal hyperplasia and transepidermal water loss were observed in WD-fed vs control mice. Th17 cytokine upregulation was observed in the ear skin of WD-fed mice; within 2 weeks of feeding, mRNA expression of Il17a, the interleukin 17A (IL-17A) protein coding gene, increased 60-fold. Other key psoriatic disease mediators were upregulated in the ear skin of WD mice, including neutrophil chemoattractants, antimicrobial peptides, and tumor necrosis factor-α. WD-fed mice also had significantly greater frequency and absolute number of γδ T cells in the cervical lymph nodes compared with control mice. The γδ T cells from WD-fed mice displayed higher IL-23 receptor expression and potential to produce IL-17A after stimulation of IL-23. In T-cell receptor delta chain knockout mice (mice without γδ T cells), less erythema and scaling were observed in 4 weeks of WD feeding compared with wild-type mice fed the same diet. The γδ T-cell-deficient mice also displayed reduced IL-17A expression compared with wild-type mice. As such, investigators concluded that γδ T cells are an essential component to IL-17 expression and psoriatic inflammation. In CCR6-deficient mice, marked suppression of proinflammatory markers was observed, suggesting that γδ T cells and CCR6 are required for complete expression of WD-induced inflammation. Supplementation with CSM was associated with decreased erythema and scaling, and less inflammation overall.

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These data demonstrate that the Western diet can induce proinflammatory changes in as little as 4 weeks before the development of obesity. Supplementation with bile acid sequestrants appeared to stem these changes, suggesting that bile acid signaling pathways may be mediators in the relationship between diet and PsD. Disruption of IL-23 expression also appears significant in the development of PsD. The investigators believe that further research should explore the mechanisms through which WD exposure dysregulates IL-23 and bile acid pathways.

Reference

Shi Z, Wu X, Yu S, et al. Short-term exposure to a Western diet induces psoriasiform dermatitis by promoting accumulation of IL-17A-producing γδ T cells [published online February 5, 2020]. J Invest Dermatol. doi:10.1016/j.jid.2020.01.020

This article originally appeared on Dermatology Advisor