Original Article

JOURNAL OF BACTERIOLOGY AND VIROLOGY. 31 December 2024. 367-378
https://doi.org/10.4167/jbv.2024.54.4.367

ABSTRACT


MAIN

INTRODUCTION

Psoriasis is a chronic inflammatory skin disease that affects 2–4% of the global population (1). Clinically, psoriasis is characterized by red plaques with silvery scales (2). These features are associated with hyperproliferative keratinocytes and parakeratosis, indicating the presence of cell nuclei within the stratum corneum (3). In addition to these epidermal changes, psoriasis is accompanied by inflammatory dermal activity, represented by the infiltration of innate and adaptive immune cells (4). Chronic activation of the immune system and release of inflammatory cytokines in psoriasis result in damage to multiple tissues beyond the skin (5). Patients with psoriasis often exhibit inflammatory conditions affecting the joints, intestine, and central nervous system (6). Notably, metabolic syndrome—including obesity, hypertension, diabetes mellitus, and hyperlipidemia—is one of the most significant comorbidities in patients with psoriasis (5).

Metabolic syndrome-associated changes, such as increased production of inflammatory cytokines, adipocytokine secretion from adipose tissue, and intestinal microbiota dysbiosis, are potential pathological mechanisms linking metabolic syndrome and psoriasis (7, 8). Notably, these changes are primarily influenced by unhealthy diets high in fat and sugar (9). In mice, a high-fat diet (HFD) containing saturated or trans-unsaturated fatty acids is widely used to induce obesity (10). Although containing less fat than an HFD, a typical Western diet (WD) is rich in fats and simple sugars that include sucrose (9). Accumulating evidence has independently demonstrated the exacerbation of psoriatic skin inflammation by various types of diets, including those high in fat, fat and sugar, and saturated fatty acids (9, 10, 11, 12). However, no comprehensive analysis has fully addressed the inflammatory responses in the skin and intestine according to these diet types, which critically influence these tissues.

In this study, we examined the effects of HFD- and WD-induced inflammatory changes in the skin and small intestine using a murine model of psoriasis induced by topical application of imiquimod (IMQ). We assessed inflammatory responses in the skin, measured serum levels of inflammatory mediators, and analyzed immune environment changes in the small intestine. To gain insight into how different types of diets influence inflammatory responses in the skin, we compared transcriptomic changes in the skin lesions of mice with psoriatic inflammation following HFD or WD.

MATERIALS AND METHODS

Mice

C57BL/6 male mice purchased from Orient Bio (Gyeonggi-do, Korea) were maintained at standard temperature and humidity in a specific pathogen-free environment. All procedures involving mice were reviewed and approved by the Center of Animal Care and Use of the Lee Gil Ya Cancer and Diabetes Institute, Gachon University (Approval number: LCDI-2020-0113). Mice were fed one of three diets for 12 weeks. The HFD contained 60 kcal% from fat, 20 kcal% from carbohydrate, and 275.2 kcal from sucrose (Research Diets, New Brunswick, NJ, USA). The WD contained 58 kcal% from fat, 25.5 kcal% from carbohydrate, and 700 kcal from sucrose (Research Diets). The standard chow diet contained 24.6 kcal% from fat, 54.6 kcal% from carbohydrate, and 12.72 kcal from sucrose (LabDiet, St. Louis, MO, USA). After 12 weeks, fasting glucose levels were measured using a glucometer (Allmedicus, Kyunggi, Korea) following fasting for 18 h. At sacrifice, blood samples, skin, perigonadal adipose tissue, spleen, small intestine, and cecal contents were collected for subsequent analyses.

Animal model of experimental psoriasis

A topical dose of 62.5 mg IMQ cream (5%, Aldara™; 3M Pharmaceuticals, Maplewood, MN, USA) or vehicle cream (Vaseline; Unilever, Rotterdam, Netherlands) was applied to the shaved back of mice for 5 days. Mice were assessed daily for changes in body weight. Transepidermal water loss (TEWL) was measured on the back skin using a Tewameter TM210 instrument (Courage + Khazaka GmbH, Cologne, Germany). Erythema and scaling were scored independently from 0–3 (0, none; 1, slight; 2, moderate; 3, marked).

Enzyme-linked immunosorbent assay (ELISA)

A Quantikine Mouse CD14 ELISA Kit (R&D Systems, Minneapolis, MN, USA) was used to measure the serum levels of soluble CD14 (sCD14) according to the instructions provided by the manufacturer. Absorbances of sCD14 were measured at 450 nm using the VICTOR X4 instrument (PerkinElmer, Waltham, MA, USA).

Quantitative polymerase chain reaction (PCR)

RNA was isolated from the skin and small intestine of mice using QIAzol and purified using an RNeasy mini kit (Qiagen, Hilden, Germany). The purified RNA was processed with DNase I (New England Biolabs, Ipswich, MA, USA) to remove genomic DNA. Complementary DNA (cDNA) was synthesized using an iScript™ cDNA synthesis kit (Bio-Rad Laboratories, Hercules, CA, USA). Quantitative PCR was performed using iQ SYBR® Green Supermix (Bio-Rad Laboratories) on a CFX Connect™ real-time PCR detection system (Bio-Rad Laboratories). Relative gene expression was determined using the 2−ΔΔCt method, with glyceraldehyde 3-phosphate dehydrogenase gene (Gapdh) served as an invariant control. The primer sequences are presented in Supplementary Table 1.

Microbiota analysis

Genomic DNA was isolated from fresh or frozen cecal contents using the QIAamp Fast DNA Stool Kit (Qiagen). The amounts of 16S rRNA gene sequences for each bacterial phylum were quantified by real-time PCR analysis and normalized to the total amount of eubacterial 16S rRNA genes in the sample. The primer sequences are shown in Supplementary Table 1.

RNA extraction, library construction, and sequencing

Total RNA concentration was calculated using Quant-IT RiboGreen (Invitrogen, Waltham, MA, USA). To determine the percentage of RNA fragments > 200 bp (DV200), samples were analyzed on the TapeStation RNA screentape (Agilent, Santa Clara, CA, USA), with a DV200 value ≥ 50%. A total of 100 ng of total RNA was used for sequencing library construction, employing the SureSelectXT RNA Direct Library Preparation Kit (Agilent). The human exonic regions were captured using the SureSelect XT Mouse All Exon Kit (Agilent). Indexed libraries were submitted for sequencing on a NovaSeqX platform (Illumina, San Diego, CA, USA), with paired-end sequencing performed by Macrogen (Seoul, Korea).

Sequence annotation and statistical analysis of gene expression

Raw reads were preprocessed to remove low-quality and adapter sequences. The processed reads were aligned to the mm10 mouse genome reference using HISAT v2.1.0. Subsequently, aligned reads were assembled into transcripts using StringTie v2.1.3b, and their abundance was estimated. Genes with read counts of zero in one or more samples were excluded. Principal component analysis (PCA) plots were generated to confirm the similarity of expression among the samples. The statistical significance of the differential expression data was determined using the nbinomWaldTest with DESeq2. Significant gene list was filtered by |fold change| ≥ 2 and raw p-value < 0.05. All data analyses and visualizations of differentially expressed genes (DEGs) were performed using R 4.2.2 (www.r-project.org).

Gene set enrichment analysis (GSEA)

GSEA was performed using the GSEA v4.3.2 software provided by the Broad Institute (Cambridge, MA, USA) as previously described (13). Enrichment analysis was performed using the hallmark gene sets from the MsigDB database. To determine the enrichment of ontology gene sets (C5.all.v2022.1), mouse gene symbols were remapped to human orthologs. Leading-edge analysis was performed to determine the overlapping gene sets. Selected gene sets with p < 0.05 and false discovery rate < 0.25 were considered.

Graphical illustrations

Schematics of experimental workflows were created using a licensed version of Biorender.com.

Statistical analyses

Data differences between groups were examined for statistical significance using one-way analysis of variance (ANOVA) with the Tukey post hoc or Kruskal–Wallis test with Dunn’s multiple comparison test. Multiple comparison tests were performed using a two-way ANOVA with Bonferroni’s multiple comparisons test. A p-value < 0.05 was considered significant. GraphPad Prism 10.3.1 (GraphPad, San Diego, CA, USA) was used for the data analyses.

RESULTS

Diet-induced metabolic changes aggravate psoriatic inflammation

To induce metabolic changes, mice were fed either the HFD or WD for 12 weeks (Fig. 1A). Both diets increased body weight and perigonadal fat mass compared to the chow-diet-fed group, with greater weight gain in HFD-fed mice than that in WD-fed mice (Fig. 1B). Additionally, a significant increase in fasting glucose was observed only in the HFD-fed group, indicating that obesity-associated metabolic changes were predominantly induced by the high-fat content. The mice were subsequently topically treated with IMQ (Fig. 1A) to induce experimental psoriatic dermatitis (14). Erythema and scaling were evident in all diet groups (Fig. 2A). However, WD-fed mice showed a significant decrease in weight on day 5 of IMQ application, which was associated with an increased tendency for TEWL, erythema, and scale scores on day 6 (Fig. 2B).

https://cdn.apub.kr/journalsite/sites/jbv/2024-054-04/N0290540409/images/JBV_2024_v54n4_367_f001.jpg
Fig. 1

Obesity-associated profiles altered by diets. (A) Schematic of experimental psoriasis induced by imiquimod (IMQ) after 12 weeks of chow, high-fat (HFD), or Western diet (WD). (B) Body weight, fat mass, and fasting glucose values of mice. Data are presented as the mean ± SD. **p < 0.01 and ****p < 0.0001 using one-way ANOVA or Kruskal–Wallis test (fat mass).

https://cdn.apub.kr/journalsite/sites/jbv/2024-054-04/N0290540409/images/JBV_2024_v54n4_367_f002.jpg
Fig. 2

Clinical symptoms of psoriasis in mice treated with imiquimod (IMQ). (A) Photographs of skin lesions. HFD, high-fat diet; WD, western diet. (B) Weight changes, transepithelial water loss (TEWL), erythema, and scale of IMQ treated skin in mice (n = 11 per group). Data are presented as the mean ± SD. *, Chow IMQ vs. WD IMQ; #, Chow IMQ vs. HFD IMQ; $, HFD IMQ vs. WD IMQ. *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 using two-way ANOVA.

Systemic signs of inflammation are comparable between HFD- and WD-fed mice with psoriatic inflammation

Weight loss observed in IMQ treated mice is indicative of a systemic inflammatory response (14). As WD-fed mice exhibited an increased tendency of weight loss compared to HFD-fed mice, we assessed spleen weight as a reflection of systemic inflammation. Compared to chow-fed mice, spleen weights were increased in mice with experimental psoriasis fed either HFD or WD, with no significant differences between these two diets (Fig. 3). Patients with psoriasis have increased serum levels of sCD14 compared to healthy controls (15). Serum sCD14 levels are recognized as a marker linking inflammation between the skin and increased intestinal permeability (16). In mice with experimental psoriasis, serum sCD14 levels were increased by both HFD and WD (Fig. 3). Although the WD group showed the highest levels compared to the chow and HFD groups, no significant difference was observed between WD and HFD-fed mice. Collectively, these results indicate that both HFD and WD increased systemic inflammation in psoriatic mice compared to the chow diet. However, the extent of promoted systemic inflammation was not significantly different between these two diets.

https://cdn.apub.kr/journalsite/sites/jbv/2024-054-04/N0290540409/images/JBV_2024_v54n4_367_f003.jpg
Fig. 3

Systemic signs of inflammation. Weight of the spleen (left) and serum concentrations of soluble CD14 (sCD14). Data are presented as the mean ± SD. *p < 0.05 and **p < 0.01 using one-way ANOVA.

WD-fed mice exhibit increased expression of psoriasis-related inflammatory mediators compared to HFD-fed group

Our hypothesis that the type of diet affects localized inflammatory responses in the skin lesions of mice with psoriatic inflammation was addressed by examining mRNA expression of inflammatory mediators implicated in psoriasis pathology. Both HFD- and WD-fed mice with psoriatic inflammation showed a significant increase in the gene expression of innate immune mediators (S100a8 and Il1b), the chemokine responsible for neutrophil recruitment (Cxcl1), and the cytokine that is critical in psoriasis pathogenesis (Il22) compared to the chow-fed mice (Fig. 4). Notably, S100a8 and Cxcl1 expressions were significantly increased in the skin lesions of the WD group compared to that of the HFD group (Fig. 4). Additionally, significant increases in Il23 and Il17a expression, which are cytokines crucial for the initiation and progression of psoriasis, were observed only in the skin lesions of the WD-fed group compared to that of the chow diet-fed mice (Fig. 4). These results suggest that WD has a pronounced role in promoting psoriatic inflammation over other types of diets.

https://cdn.apub.kr/journalsite/sites/jbv/2024-054-04/N0290540409/images/JBV_2024_v54n4_367_f004.jpg
Fig. 4

Expression of inflammatory mediators in the skin. Quantitative polymerase chain reaction analysis of the skin. Data are presented as the mean ± SD. *p < 0.05, **p < 0.01, and ****p < 0.0001 using one-way ANOVA or Kruskal–Wallis test (Il1b).

Small intestinal immune environments are comparable between HFD- and WD-fed mice with psoriatic inflammation

Absorption of nutrients occurs exclusively in the small intestine, where numerous immunocompetent cells reside (17). Additionally, increased permeability of the intestinal barrier amplifies inflammatory responses beyond the intestinal tract (18). Therefore, we analyzed whether the expression of inflammatory mediators and epithelial tight junction molecules in the small intestine of mice with psoriatic inflammation was affected by different diets. As shown in Fig. 5A, the expressions of innate mediators (S100a8, Il1b, Il6, and Tnf) and tight junction molecules (Tjp1 and Tjp2) were comparable among chow-, HFD-, and WD-fed groups. The HFD and WD groups showed decreased expressions of Il23 and Il17a compared to chow-fed mice, with no significant difference between the HFD and WD groups (Fig. 5A). Next, we assessed the luminal microbiome composition by performing real-time PCR analysis of bacterial phyla in fecal samples collected from the ceca. Bacteroidetes and Firmicutes are two major phyla of the stool microbiome (19). The proportion of Bacteroidetes remained unchanged by both HFD- and WD-fed groups (Fig. 5B). Both diets decreased the proportion of Firmicutes compared to the chow diet, with no significant differences between the two diet groups (Fig. 5B). The proportional changes observed for Actinobacteria and Gamma/delta proteobacteria were similar to those observed for Firmicutes (Fig. 5B).

https://cdn.apub.kr/journalsite/sites/jbv/2024-054-04/N0290540409/images/JBV_2024_v54n4_367_f005.jpg
Fig. 5

Expression of inflammatory mediators and epithelial tight junction molecules in the small intestine. (A) Quantitative polymerase chain reaction (PCR) analysis of the small intestine. (B) Quantitative PCR analysis of cecal microbiota. Data are presented as the mean ± SD. *p < 0.05 and **p < 0.01 using one-way ANOVA or Kruskal–Wallis test (Il17a in A).

WD-fed mice with psoriatic inflammation exhibit differential transcriptomic changes in skin lesions compared to the HFD-fed mice

As WD-fed mice exhibited pronounced inflammatory changes in the skin compared to the HFD-fed mice, we compared transcriptome profiles of skin lesions between these two groups to better understand the details of inflammatory parameters influenced by diets. We identified 701 DEGs between the HFD- and WD-fed groups. Of these, 245 were upregulated and 456 were downregulated in WD-fed mice compared to that in HFD group (Supplementary Fig. 1A). PCA revealed marked differences between the two groups (Supplementary Fig. 1B). GSEA revealed enriched gene sets in HFD-fed mice associated with tissue microenvironment remodeling, including gene ontologies involved in cancer development, stem cell upregulation, and extracellular matrix organization (Fig. 6A). In contrast, enriched gene sets in WD-fed mice were associated with skin epithelial formation (keratinization and formation of the cornified envelope) and increased inflammation, such as interleukin (IL)-4 and IL-13 signaling, and tumor necrosis factor (TNF) targets, and IL-2 signaling (Fig. 6A and B). Psoriatic inflammatory genes (Il17a and Il17f) and genes associated with epithelial cell differentiation and proliferation (Sprr2e and Spdef) were among the most upregulated genes in skin lesions of WD-fed mice (Fig. 6C). In contrast, the expression of Trem2, a gene associated with obese adipose tissue metabolism, was among the most significantly downregulated genes in these mice (Fig. 6C). These results suggest that WD triggers exacerbated inflammatory responses in psoriatic skin, while attenuating responses associated with obesity-induced microenvironmental changes, compared to HFD upon IMQ treatment.

https://cdn.apub.kr/journalsite/sites/jbv/2024-054-04/N0290540409/images/JBV_2024_v54n4_367_f006.jpg
Fig. 6

Differential transcriptomic changes in the skin. (A) Gene ontology terms enriched in the skin of high-fat diet (HFD)- and western diet (WD)-fed mice treated with imiquimod (IMQ) determined by gene set enrichment analysis. (B) Selected gene sets differentially expressed in the skin (adjusted p < 0.05). The heatmaps show the log2-fold change relative to the geometric mean fragments per kilobase of exon per million fragments + 0.01. (C) Volcano plot of differentially expressed genes between HFD- and WD-fed mice treated with IMQ.

DISCUSSION

This study demonstrated that the WD induces markedly increased psoriatic inflammation compared to the HFD, even though both diets promote systemic inflammation and metabolic changes. Notably, HFD-fed mice showed greater weight gain and glucose intolerance. These findings challenge the prevailing understanding that HFD is the primary contributor to systemic inflammation and suggest that WD has unique properties that influence localized inflammatory processes, particularly in psoriatic skin lesions. Furthermore, our observations indicated that obesity alone is not sufficient to exacerbate psoriatic inflammation, highlighting dietary contents as a predisposition to accelerated psoriatic inflammation.

WD and HFD have critical differences in the composition of their nutritional content. WD typically includes high levels of sugar, processed carbohydrates, and fat, whereas HFD predominantly focuses on a high-fat content. The inclusion of refined sugars and processed components in the WD may contribute to greater systemic stress, potentiating skin inflammation. High sugar intake exacerbates inflammatory pathways by promoting systemic inflammation via activation of nucleotide-binding domain and leucine-rich repeat protein-3 and IL-1β (20), potentially inducing neutrophil chemoattracts, such as chemokine (C-X-C motif) ligand 1 (9, 21), as evidenced by the increased expression of S100a8 and Cxcl1 in WD-fed mice than that in HFD-fed mice. Additionally, the high glycemic index of WD leads to a rapid rise in blood glucose (22), resulting in insulin resistance and altered lipid metabolism. These changes may synergistically contribute to the increased severity of psoriasis (23).

Another notable observation was the differential gene expression in skin lesions between WD- and HFD-fed groups, with WD-fed mice exhibiting enrichment in gene sets related to keratinization and formation of the cornified envelope. Psoriasis is characterized by pronounced papulosquamous epithelial changes due to abnormal keratinocyte differentiation and accelerated turnover (24). The enrichment of pathways related to keratinization indicates that WD may directly impact defective keratinocyte cycles by promoting hyperproliferation and abnormal differentiation, potentially through altered lipid and carbohydrate metabolism, which affects skin barrier function. The transcriptomic analysis further highlighted that WD-fed mice had a more profound upregulation of gene sets involved in inflammatory pathways, such as IL-4, IL-13, TNF targets, and IL-2 signaling. These findings suggest that WD triggers broader immune activation, which may be responsible for exacerbating psoriatic lesions. The increased production of inflammatory mediators may also facilitate a more potent inflammatory response, contributing to impaired skin barrier function and increased susceptibility to inflammation. Interestingly, while both HFD and WD increased systemic markers of inflammation, such as spleen weight and serum sCD14, no significant differences were observed between the two diets, suggesting that the heightened psoriatic inflammation in WD-fed mice involves localized factors rather than an increase in systemic inflammation. This further suggests that specific components of WD may more effectively disrupt skin homeostasis, leading to increased sensitivity and exaggerated inflammatory responses. One such component could be advanced glycation end-products (AGEs), which are characterized by covalent bonds between a reduced sugar and a free amino group. AGEs are abundant in the WD and have a prominent capacity to induce oxidative stress and tissue damage, thereby promoting inflammatory responses (25, 26). Additionally, WD-induced dysregulated bile acid signaling contributes to cutaneous inflammation by inducing T helper type 17-mediated skin inflammation (11, 27).

The role of the gut-skin axis may also be crucial in explaining the differential impacts of WD and HFD. Increased intestinal permeability, influenced by dietary composition, can lead to systemic endotoxemia, which has been linked to skin inflammation. WD induces a shift in gut microbiota composition, enhancing susceptibility to bacterial infection and intestinal inflammation (28). However, we observed no significant differences in the intestinal immune environment or microbiome composition between the WD and HFD groups. Additionally, intestinal expression of inflammatory mediators and epithelial junctional molecules was comparable between these two groups, suggesting that while gut permeability may contribute to systemic inflammation, the localized effects of WD on skin inflammation probably involve additional mechanisms independent of gut immune environmental changes.

Overall, our data suggest that the WD exacerbates psoriatic inflammation due to a combination of factors, including increased metabolic stress, alterations in keratinocyte differentiation, and upregulation of skin-specific inflammatory pathways. These findings emphasize the need for considering dietary components beyond fat content alone when evaluating diet-induced exacerbation of inflammatory skin conditions such as psoriasis. Future studies should focus on elucidating specific components of WD that drive these changes and exploring potential interventions to mitigate diet-induced inflammatory responses in psoriasis.

SUPPLEMENTARY DATA

https://cdn.apub.kr/journalsite/sites/jbv/2024-054-04/N0290540409/images/JBV_2024_v54n4_367_f007.jpg
Supplementary Fig. 1

Differential enrichment of gene expression in the skin. (A) Heat map of one-way hierarchical clustering based on differentially expressed genes among the indicated treatment groups (fold change ≥ 2, p < 0.05). (B) Score plots of principal component (PC) analysis based on the differentially expressed genes between the indicated treatment groups.

Supplementary Table 1.

Primer sequences for RT-PCR

Target genes Primer sequences
S100a8 Forward: 5′-TTC CTT GCG ATG GTG ATA-3′
Reverse: 5′-ATG ATG ACT TTA TTC TGT AGA CA-3′
Il1b Forward: 5′-GCA ACT GTT CCT GAA CTC AAC T-3′
Reverse: 5′-ATC TTT TGG GGT CCG TCA AC-3′
Il6 Forward: 5′- TAG TCC TTC CTA CCC CAA TT -3′
Reverse: 5′- TTG GTC CTT AGC CAC TCC TTC -3′
Tnf Forward: 5′-CCT GTA GCC CAC GTC GTA G-3′
Reverse: 5′-GGG AGT AGA CAA GGT ACA ACC C-3′
Cxcl1 Forward: 5′-AGT CAT AGC CAC ACT CAA GAA T-3′
Reverse: 5′-TCA GAA GCC AGC GTT CAC-3′
Il22 Forward: 5′-ACC AGA ACA TCC AGA AGA AT-3′
Reverse: 5′-CTC AGA CGC AAG CAT TTC-3′
Il23 Forward: 5′-CTA AGA GAA GAA GAG GAT GAA GAG-3′
Reverse: 5′-CTG GCT GTT GTC CTT GAG-3′
Il17a Forward: 5′-GAC TTC CTC CAG AAT GTG AA-3′
Reverse: 5′-TGG AAC GGT TGA GGT AGT-3′
Tjp1 Forward: 5′- ACC TCT ACT CTA CGA CAT -3′
Reverse: 5′- GTG GAA CTT GCT CAT AAC -3′
Tjp2 Forward: 5′- GTG GAG TGG TTC GGT TGA -3′
Reverse: 5′- TGA GTG TAG TTG AGC AGG TC -3′
Gapdh Forward: 5′-CTG GTA TGA CAA TGA ATA CGG-3′
Reverse: 5′-GCA GCG AAC TTT ATT GAT GG-3′
Bacteroidetes Forward: 5′- GTT TAA TTC GAT ACG CGA G -3′
Reverse: 5′- TTA ASC CGA CAC CTC ACG G -3′
Firmicutes Forward: 5′- GGA GYA TGT GGT TTA ATT CGA AGC A -3′
Reverse: 5′- AGC TGA CGA CAA CCA TGC AC -3′
Actinobacteria Forward: 5′- TGT AGC GGT GGA ATG CGC -3′
Reverse: 5′- AAT TAA GCC ACA TGC TCC GCT -3′
Gamma and Delta proteobacteria Forward: 5′- GCT AAC GCA TTA AGT RYC CCG-3′
Reverse: 5′- GCC ATG CRG CAC CTG TCT -3′
Eubacteria Forward: 5′- AAA CTC AAA KGA ATT GAC GG -3′
Reverse: 5′- CTC ACR RCA CGA GCT GAC -3′

* Nucleotide symbols: R = ‘A’ or ‘G,’ Y = ‘C’ or ‘T,’ N = any nucleotide, W = ‘A’ or ‘T,’ M = ‘A’ or ‘C,’ K = ‘T’ or ‘G,’ S = ‘C’ or ‘G,’ and H = ‘A’/’C’/’T’

AUTHOR CONTRIBUTION

YJ conceived the project, designed the experiments, and interpreted the data. MP and KP acquired, analyzed, and interpreted the data. MP and YJ wrote the first draft of the manuscript. All authors contributed to the manuscript, finalized it, and approved the article for publication.

CONFLICT OF INTEREST

The authors declare that they have no competing interests.

Acknowledgements

This study was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (NRF-2021R1A5A2030333 and 2023R1A2C2002522).

References

1

Christophers E. Psoriasis--epidemiology and clinical spectrum. Clin Exp Dermatol. 2001;26(4):314-320.

10.1046/j.1365-2230.2001.00832.x11422182
2

Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370(9583):263-271.

10.1016/S0140-6736(07)61128-317658397
3

Balan R, Grigoraş A, Popovici D, Amălinei C. The histopathological landscape of the major psoriasiform dermatoses. Arch Clin Cases. 2021;6(3):59-68.

10.22551/2019.24.0603.1015534754910PMC8565680
4

Kim HJ, Roh JY, Jung Y. Eosinophils accelerate pathogenesis of psoriasis by supporting an inflammatory milieu that promotes neutrophil infiltration. J Invest Dermatol. 2018;138(10):2185-2194.

10.1016/j.jid.2018.03.150929580867
5

Hao Y, Zhu YJ, Zou S, Zhou P, Hu YW, Zhao QX, et al. Metabolic Syndrome and Psoriasis: Mechanisms and Future Directions. Front Immunol. 2021;12:711060.

10.3389/fimmu.2021.71106034367173PMC8343100
6

Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker JNWN. Psoriasis. Lancet. 2021;397(10281):1301-1315.

10.1016/S0140-6736(20)32549-633812489
7

Mathis D. Immunological goings-on in visceral adipose tissue. Cell Metab. 2013;17(6):851-859.

10.1016/j.cmet.2013.05.00823747244PMC4264591
8

Chen YJ, Ho HJ, Tseng CH, Lai ZL, Shieh JJ, Wu CY. Intestinal microbiota profiling and predicted metabolic dysregulation in psoriasis patients. Exp Dermatol. 2018;27(12):1336-1343.

10.1111/exd.1378630238519
9

Yu S, Wu X, Zhou Y, Sheng L, Jena PK, Han D, et al. A Western Diet, but Not a High-Fat and Low-Sugar Diet, Predisposes Mice to Enhanced Susceptibility to Imiquimod-Induced Psoriasiform Dermatitis. J Invest Dermatol. 2019;139(6):1404-1407.

10.1016/j.jid.2018.12.00230571973PMC7574630
10

Nakamizo S, Honda T, Adachi A, Nagatake T, Kunisawa J, Kitoh A, et al. High fat diet exacerbates murine psoriatic dermatitis by increasing the number of IL-17-producing gammadelta T cells. Sci Rep. 2017;7(1):14076.

10.1038/s41598-017-14292-129074858PMC5658347
11

Shi Z, Wu X, Yu S, Huynh M, Jena PK, Nguyen M, et al. Short-Term Exposure to a Western Diet Induces Psoriasiform Dermatitis by Promoting Accumulation of IL-17A-Producing gammadelta T Cells. J Invest Dermatol. 2020;140(9):1815-1823.

10.1016/j.jid.2020.01.02032057839PMC7537492
12

Herbert D, Franz S, Popkova Y, Anderegg U, Schiller J, Schwede K, et al. High-Fat Diet Exacerbates Early Psoriatic Skin Inflammation Independent of Obesity: Saturated Fatty Acids as Key Players. J Invest Dermatol. 2018;138(9):1999-2009.

10.1016/j.jid.2018.03.152229605673
13

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545-15550.

10.1073/pnas.050658010216199517PMC1239896
14

van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182(9):5836-5845.

10.4049/jimmunol.080299919380832
15

Kim HJ, Jang J, Na K, Lee EH, Gu HJ, Lim YH, et al. TLR7-dependent eosinophil degranulation links psoriatic skin inflammation to small intestinal inflammatory changes in mice. Exp Mol Med. 2024;56:1164-1177.

10.1038/s12276-024-01225-y38689088PMC11148187
16

Johnston DGW, Hambly R, Kearney N, Tobin DJ, Kirby B. A preliminary study of soluble CD14 levels in the serum of patients with hidradenitis suppurativa as a marker of "leaky gut". HRP Open Res. 2022;5(68):1-8.

10.12688/hrbopenres.13633.1
17

Jang J, Hwang S, Oh AR, Park S, Yaseen U, Kim JG, et al. Fructose malabsorption in ChREBP-deficient mice disrupts the small intestine immune microenvironment and leads to diarrhea-dominant bowel habit changes. Inflamm Res. 2023;72(4):769-782.

10.1007/s00011-023-01707-136813915
18

De Pessemier B, Grine L, Debaere M, Maes A, Paetzold B, Callewaert C. Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms. 2021;9(2):353.

10.3390/microorganisms902035333670115PMC7916842
19

Leite GGS, Weitsman S, Parodi G, Celly S, Sedighi R, Sanchez M, et al. Mapping the Segmental Microbiomes in the Human Small Bowel in Comparison with Stool: A REIMAGINE Study. Dig Dis Sci. 2020;65(9):2595-2604.

10.1007/s10620-020-06173-x32140945PMC7419378
20

Christ A, Günther P, Lauterbach MAR, Duewell P, Biswas D, Pelka K, et al. Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming. Cell. 2018;172(1-2):162-175.e14.

10.1016/j.cell.2017.12.01329328911PMC6324559
21

Amaral FA, Costa VV, Tavares LD, Sachs D, Coelho FM, Fagundes CT, et al. NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B(4) in a murine model of gout. Arthritis Rheum. 2012;64(2):474-484.

10.1002/art.3335521952942
22

Atkinson FS, Foster-Powell K, Brand-Miller JC. International Tables of Glycemic Index and Glycemic Load Values: 2008. Diabetes Care. 2008;31(12):2281-2183.

10.2337/dc08-123918835944PMC2584181
23

Christ A, Lauterbach M, Latz E. Western Diet and the Immune System: An Inflammatory Connection. Immunity. 2019;51(5):794-811.

10.1016/j.immuni.2019.09.02031747581
24

Park S, Jang J, Kim HJ, Jung Y. Unveiling multifaceted roles of myeloid innate immune cells in the pathogenesis of psoriasis. Mol Aspects Med. 2024;99:101306.

10.1016/j.mam.2024.10130639191143
25

Delgado-Andrade C. Carboxymethyl-lysine: thirty years of investigation in the field of AGE formation. Food Funct. 2016;7(1):46-57.

10.1039/C5FO00918A26462729
26

Bettiga A, Fiorio F, Di Marco F, Trevisani F, Romani A, Porrini E, et al. The Modern Western Diet Rich in Advanced Glycation End-Products (AGEs): An Overview of Its Impact on Obesity and Early Progression of Renal Pathology. Nutrients. 2019;11(8):1748.

10.3390/nu1108174831366015PMC6724323
27

Jena PK, Sheng L, McNeil K, Chau TQ, Yu S, Kiuru M, et al. Long-term Western diet intake leads to dysregulated bile acid signaling and dermatitis with Th2 and Th17 pathway features in mice. J Dermatol Sci. 2019;95(1):13-20.

10.1016/j.jdermsci.2019.05.00731213388PMC6991164
28

Agus A, Denizot J, Thévenot J, Martinez-Medina M, Massier S, Sauvanet P, et al. Western diet induces a shift in microbiota composition enhancing susceptibility to Adherent-Invasive E. coli infection and intestinal inflammation. Sci Rep. 2016;6:19032.

10.1038/srep1903226742586PMC4705701
페이지 상단으로 이동하기