Short-Term Exposure to a Western Diet Induces Psoriasiform Dermatitis by Promoting Accumulation of IL-17A–Producing γδ T Cells

Abstract

A Western diet (WD)-characterized by its high fat and simple sugar content-is thought to predispose individuals to inflammatory skin diseases such as psoriasis through the development of obesity. This scenario, however, is being challenged by emerging data suggesting that dietary components, rather than obesity itself, may exacerbate psoriasis. We herein show that short-term feeding with a diet analogous to the WD in mice leads to T helper type 1e/T helper type 17ebiased skin inflammation before significant body weight gain. Feeding for as little as 4 weeks with a WD promoted mild dermatitis and accumulation of IL-17Aeproducing gd T cells in the skin. Strikingly, gd T cells from WD-fed mice exhibited enriched IL-23 receptor expression and increased the potential to produce IL-17A after IL-23 stimulation. In contrast to wild-type mice, WD-fed TCRdedeficient and CCR6-deficient mice had reduced skin inflammation and IL-17A expression. Supplementation with a bile acid sequestrant, cholestyramine, prevented WD-induced skin inflammation along with a reduction in the infiltration of gd T cells and the expression of proinflammatory mediators. In summary, our data revealed dietary influences in inflammatory signaling in the skin. The dysregulation of IL-23 pathways and bile acid pathways may be key to the development of WD-associated psoriasiform dermatitis.

Dysregulated Bile Acid Receptor-mediated Signaling and IL-17A Induction are Implicated in Diet-associated Hepatic Health and Cognitive Function

“…Increased IL-17A is also found in mouse models of Alzheimer's diseases and hepatic brosis [42,43]. Moreover, our recent publication shows that short-term feeding of another WD leads to T helper type 1-/T helper type 17-biased skin in ammation before signi cant body weight gain is noted [31]. WD intake for 4 weeks promotes mild dermatitis and accumulation of IL-17A-producing γδ T cells in the skin.…”

“…Inulin prevents FPC diet-induced in ammatory signaling IL-17A is implicated in the development of chronic in ammatory diseases in the brain, skin, and liver as well as liver cancer [30][31][32][33]. FPC diet-fed mice had increased mRNA level of Rorγt, a transcriptional factor for Il-17 expression, accompanied by elevated hepatic protein levels of IL-17A and TNFα as well as mRNA levels of Il6, Il1β, and Tgfβ, which generate Th17 cells; inulin supplementation prevented these changes (Fig.…”

“…WD intake for 4 weeks promotes mild dermatitis and accumulation of IL-17A-producing γδ T cells in the skin. Furthermore, supplementation with cholestyramine, a BA sequestrant, can prevent skin in ammation along with a reduction in the in ltration of γδ T cells and the expression of proin ammatory mediators [31]. The differentiation of Th17 cells relies on a variety of cytokines, and transcriptional factors such as RORγt and TGFβ in synergy with IL6 are critical for generating Th17 cells [44].…”

Association of Pathogenic Th17 Cells with the Disease Severity and Its Potential Implication for Biological Treatment Selection in Psoriasis Patients

“…Psoriasis etiology is not completely understood; however, evidence has shown that the immune response is a key factor in the physiopathology due to the high quantities of inflammatory cytokines such as IL-17 and IL-22 and immune cell populations in skin lesions and peripheral blood (PB) [ 7 – 9 ]. Remarkably, Th17 lymphocytes are increased in the lesional skin and PB, contributing to the disease pathogenesis through IL-17 and IL-22 production [ 10 , 11 ]. These cytokines promote the recruitment and activation of immune cells and increase keratinocyte proliferation, respectively [ 12 , 13 ].…”

Dysregulated Bile Acid Receptor-mediated Signaling and IL-17A Induction are Implicated in Diet-associated Hepatic Health and Cognitive Function

“…Inulin prevents FPC diet-induced in ammatory signaling IL-17A is implicated in the development of chronic in ammatory diseases in the brain, skin, and liver as well as liver cancer [31][32][33][34]. FPC diet-fed mice had increased mRNA level of Rorγt, a transcriptional factor for Il-17 expression, accompanied by elevated hepatic protein levels of IL-17A and TNFα as well as mRNA levels of Il6, Il1β, and Tgfβ, which generate Th17 cells; inulin supplementation prevented these changes ( Figure 3A, B).…”