A Western Diet, but Not a High-Fat and Low-Sugar Diet, Predisposes Mice to Enhanced Susceptibility to Imiquimod-Induced Psoriasiform Dermatitis

Yu, Sebastian; Wu, Xuesong; Zhou, Yan; Sheng, Lili; Jena, Prasant Kumar; Han, Dan; Wan, Yu; Hwang, Samuel T

doi:10.1016/j.jid.2018.12.002

Cited by 40 publications

(35 citation statements)

References 18 publications

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“…Moreover, females in general have higher incidence of autoimmune disease in humans [40]. We also reported that WD-fed mice had increased susceptibility to IMQinduced psoriasiform dermatitis whereas mice on high fat diet alone did not [6] suggesting that obesity alone may be insufficient to increase the propensity of mice to cutaneous inflammation. Histologically, the dermatitis we observed in WDfed mice had epidermal hyperplasia with hypergranulosis and spongiosis typical of atopic dermatitis but also displayed intraepidermal neutrophils that are expected in classic psoriatic lesions in humans [26].…”

Section: Discussionmentioning

confidence: 72%

“…Interestingly, high fat diet-fed mice exhibit exacerbated imiquimod (IMQ)-induced dermatitis in the auricula skin, whereas obese (ob/ob) mice fed a normal diet do not show enhanced susceptibility to IMQ-induced dermatitis, indicating that obesity alone may be insufficient to enhance susceptibility to psoriasiform dermatitis [4,5]. Supporting this concept in our recent report demonstrating that more obese highfat diet-fed mice did not have enhanced susceptibility to IMQinduced dermatitis whereas less obese WD-fed mice did, suggesting that dietary components, rather than obesity alone, may influence susceptibility to IMQ dermatitis [6]. Atopic dermatitis is another chronic inflammatory skin disease that is driven by terminal keratinocyte differentiation abnormalities, and displays heterogeneity in the sense that Th2, Th22, Th17/IL-23, and Th1 cytokine pathways can be activated, depending on the disease subtype.…”

Section: Introductionmentioning

confidence: 79%

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Long-term Western diet intake leads to dysregulated bile acid signaling and dermatitis with Th2 and Th17 pathway features in mice

Jena

Sheng

McNeil

et al. 2019

Journal of Dermatological Science

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Background: Dietary interventions are implicated in the development of atopic dermatitis, psoriasis, and acne. Objective: To investigate the effect of diet and the bile acid (BA) receptors, such as TGR5 (Takeda G protein receptor 5) and S1PR2 (sphingosine-1-phosphate receptor 2) in the development of dermatitis. Methods: C57BL/6 mice were fed a control diet (CD) or Western diet (WD) since weaning until they were 10 months old followed by analyzing histology, gene expression, and BA profiling. Results: Mice developed dermatitis as they aged and the incidence was higher in females than males. Additionally, WD intake substantially increased the incidence of dermatitis. Cutaneous antimicrobial peptide genesS100A8, S100A9, and Defb4 were reduced in WD-fed mice, but increased when mice developed skin lesions. In addition, Tgr5 and TGR5-regulated Dio2 and Nos3 were reduced in WD intake but induced in dermatitic lesions. Trpa1 and Trpv1, which mediate itch, were also increased in dermatitic lesions. The expression of S1pr2 and genes encoding sphingosine kinases, S1P phosphatases, binding protein, and transporter were all reduced by WD intake but elevated in dermatitic lesions. Furthermore, dermatitis development increased total cutaneous BA with an altered profile, which may change TGR5 and S1PR2 activity. Moreover, supplementation with BA sequestrant cholestyramine reduced epidermal thickening as well as cutaneous inflammatory cytokines. Conclusion: In summary, activation of TGR5 and S1PR2, which regulate itch, keratinocyte proliferation, metabolism, and inflammation, may contribute to WD-exacerbated dermatitis with Th2 and Th17 features. In addition, elevated total BA play a significant role in inducing dermatitis and cutaneous inflammation.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 79%

Long-term Western diet intake leads to dysregulated bile acid signaling and dermatitis with Th2 and Th17 pathway features in mice

Jena

Sheng

McNeil

et al. 2019

Journal of Dermatological Science

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“…In obesity, visceral adipose tissue is a crucial site for the formation of proinflammatory adipokines such as IL-6 and TNF-a-both key cytokines implicated in the pathogenesis of psoriasis. Recently, the causative relationship between obesity and psoriatic inflammation is being challenged by emerging data implicating that dietary components, rather than obesity itself, may exacerbate psoriasis (Herbert et al, 2018;Nakamizo et al, 2017;Yu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

“…Long-term intake of WD leads to dysregulated bile acid (BA) signaling accompanied by dysbiosis, which is implicated in WD-exacerbated dermatitis as well as other metabolically compromised phenotypes (Jena et al, 2017;Sheng et al, 2017). In particular, it is the WD, rather than a high-fat diet (HFD), that enhances susceptibility of mice to imiquimod-induced psoriasiform dermatitis (PsD), suggesting obesity alone is not sufficient to promote psoriatic inflammation (Yu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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

Shi

et al. 2020

Journal of Investigative Dermatology

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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.

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“…The extent of the skin reaction to imiquimod differs among mouse strains, with females being most sensitive in all cases (Alvarez & Jensen, 2016;Swindell et al, 2017). It is also possible that the extent of imiquimod-induced psoriasiform skin inflammation is dependent on the general health of the animal (e.g., body weight), which might explain variations in response to the irritant (Yu et al, 2019(Yu et al, , 2020. Given these factors, all experiments should be repeated at least three times to obtain the most robust and reliable findings.…”

Section: Understanding Resultsmentioning

confidence: 99%

A Localized Aldara (5% Imiquimod)–Induced Psoriasiform Dermatitis Model in Mice Using Finn Chambers

et al. 2020

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The expanding number of research studies utilizing the imiquimod‐induced psoriasiform dermatitis model attests to the usefulness of this procedure. Advantages of this model include rapid development of the skin response and cost‐effectiveness. A major limitation is that application of imiquimod cream over large areas of skin, as well as licking and ingestion of the cream, may lead to severe systemic inflammation, which can cause a general decline in health, splenomegaly, and death. In this protocol, Finn chambers are used to localize the imiquimod cream to a small area of the skin. This results in production of severe and reproducible psoriatic skin reactions with significantly less imiquimod, greatly reducing the possibility of untoward systemic effects. Moreover, having psoriasiform and control skin areas on the same mice decreases inter‐animal differences. The protocol can be readily adapted for other skin disease models involving topical application of test agents. This article also details functional measurements performed during assays, including skin thickness, blood perfusion, semiquantitative histopathological evaluation, determination of scaling score to monitor psoriatic symptoms, and collection of spleen and body weight data to identify systemic effects. © 2020 The Authors. Basic Protocol: Use of Finn chambers to induce psoriasiform skin reactions with imiquimod Support Protocol 1: Measurement of double‐fold dorsal skin thickness Support Protocol 2: Measurement of blood perfusion Support Protocol 3: Determination of scaling score Support Protocol 4: Semiquantitative histopathological scoring Support Protocol 5: Assessment of systemic side effects in response to imiquimod application

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A Western Diet, but Not a High-Fat and Low-Sugar Diet, Predisposes Mice to Enhanced Susceptibility to Imiquimod-Induced Psoriasiform Dermatitis

Cited by 40 publications

References 18 publications

Long-term Western diet intake leads to dysregulated bile acid signaling and dermatitis with Th2 and Th17 pathway features in mice

Long-term Western diet intake leads to dysregulated bile acid signaling and dermatitis with Th2 and Th17 pathway features in mice

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

A Localized Aldara (5% Imiquimod)–Induced Psoriasiform Dermatitis Model in Mice Using Finn Chambers

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