Discovery and preclinical evaluation of KYS202004A, a novel bispecific fusion protein targeting TNF-α and IL-17A, in autoimmune disease models.

The treatment of autoimmune and inflammatory diseases often requires targeting multiple pathogenic pathways. KYS202004A is a novel bispecific fusion protein designed to antagonize TNF-α and IL-17A, pivotal in the pathophysiology of autoimmune and inflammatory diseases. Our initial efforts focused on screening for optimal structure by analyzing expression levels, purity, and binding capabilities. The binding affinity of KYS202004A to TNF-α and IL-17A was evaluated using SPR. In vitro, we assessed the inhibitory capacity of KYS202004A on cytokine-induced CXCL1 expression in HT29 cells. In vivo, its efficacy was tested using a Collagen-Induced Arthritis (CIA) model in transgenic human-IL-17A mice and an imiquimod-induced psoriasis model in cynomolgus monkeys. KYS202004A demonstrated significant inhibition of IL-17A and TNF-α signaling pathways, outperforming the efficacy of monotherapeutic agents ixekizumab and etanercept in reducing CXCL1 expression in vitro and ameliorating disease markers in vivo. In the CIA model, KYS202004A significantly reduced clinical symptoms, joint destruction, and serum IL-6 concentrations. The psoriasis model revealed that KYS202004A, particularly at a 2  mg/kg dose, was as effective as the combination of ixekizumab and etanercept. This discovery represents a significant advancement in treating autoimmune and inflammatory diseases, offering a dual-targeted therapeutic approach with enhanced efficacy over current monotherapies.

Biologics targeting IL-17 sharply reduce circulating T follicular helper and T peripheral helper cell sub-populations in psoriasis.

Introduction: Circulating T follicular helper (cTfh) cells and circulating T peripheral helper (cTph) cells (which share common characteristics with the cTfh population) are implicated in the pathogenesis of immune-mediated and autoimmune diseases such as psoriasis (Ps). Their close interplay with the interleukin 17 (IL-17) axis and the ex vivo effect of IL-17-targeting biologic agents used to treat Ps on them are elusive. This study aimed to investigate the effect of biologics targeting IL-17 on cTfh and cTph cell subpopulations isolated from the blood of patients with Ps. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with Ps at treatment initiation and three months later. Samples were also collected from controls. Cells were stained using monoclonal antibodies. Flow cytometry assessed the fraction of cTfh (CD3+CD4+CXCR5+) and cTph (CD3+CD4+CXCR5-PD-1hi) cells.. Results: Flow cytometric analysis showed increased fractions of activated cTfh subsets including ICOS+ and ICOS+PD-1+ expressing cells, in patients compared to controls. Biologic blocking of IL-17A diminished the cTfh population. Furthermore, ICOS+ and ICOS+PD-1+ sub-populations were also inhibited. Finally, the cTph cell fraction significantly decreased after three months of successful treatment with biologics. Conclusion: Early anti-IL-17-mediated clinical remission in Ps is associated with decreased cTfh and cTph cell subpopulations.

Extracellular vescicles in psoriasis: from pathogenesis to possible roles in therapy.

Psoriasis is a chronic inflammatory disease affecting skin and joints characterized by a chronically altered immune and inflammatory response. Several factors occur from the onset to the development of this disease due to different types of cells spatially and temporally localized in the affected area, such as, keratinocytes, macrophages, neutrophils and T helper lymphocytes. This scenario leads to the chronic release of high levels of inflammatory mediators (i.e., IL-17, IL-23, IL-22, TNF-α, S100 proteins, Defensins) and lastly parakeratosis and thickening of the stratum spinosum. Extracellular vesicles (EVs) are small double membraned biological nanoparticles that are secreted by all cell types and classified, based on dimension and biogenesis, into exosomes, microvesicles and apoptotic bodies. Their role as vessels for long range molecular signals renders them key elements in the pathogenesis of psoriasis, as well as innovative platforms for potential biomarker discovery and delivery of fine-tuned anti-inflammatory therapies. In this review, the role of EVs in the pathogenesis of psoriasis and the modulation of cellular microenvironment has been summarized. The biotechnological implementation of EVs for therapy and research for new biomarkers has been also discussed.

Granzyme K mediates IL-23-dependent inflammation and keratinocyte proliferation in psoriasis.

Psoriasis is an inflammatory disease with systemic manifestations that most commonly presents as itchy, erythematous, scaly plaques on extensor surfaces. Activation of the IL-23/IL-17 pro-inflammatory signaling pathway is a hallmark of psoriasis and its inhibition is key to clinical management. Granzyme K (GzmK) is an immune cell-secreted serine protease elevated in inflammatory and proliferative skin conditions. In the present study, human psoriasis lesions exhibited elevated GzmK levels compared to non-lesional psoriasis and healthy control skin. In an established murine model of imiquimod (IMQ)-induced psoriasis, genetic loss of GzmK significantly reduced disease severity, as determined by delayed plaque formation, decreased erythema and desquamation, reduced epidermal thickness, and inflammatory infiltrate. Molecular characterization in vitro revealed that GzmK contributed to macrophage secretion of IL-23 as well as PAR-1-dependent keratinocyte proliferation. These findings demonstrate that GzmK enhances IL-23-driven inflammation as well as keratinocyte proliferation to exacerbate psoriasis severity.

Modulation of the skin and gut microbiome by psoriasis treatment: a comprehensive systematic review.

The microbiome is intricately linked to the development of psoriasis, serving as both a potential cause and consequence of the psoriatic process. In recent years, there has been growing interest among psoriasis researchers in exploring how psoriasis treatments affect the skin and gut microbiome. However, a comprehensive evaluation of the impact of modern treatment approaches on the microbiome has yet to be conducted. In this systematic review, we analyze studies investigating alterations in the skin and gut microbiome resulting from psoriasis treatment, aiming to understand how current therapies influence the role of the microbiome in psoriasis development. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed and Scopus databases were searched for eligible studies from the inception dates until July 5, 2023. Study selection, data extraction, and risk of bias assessment were carried out by three overlapping pairs of reviewers, resolving any disagreements through consensus. Our analysis of various treatments, including biologics, conventional medications, phototherapy, and probiotics, reveals significant shifts in microbial diversity and abundance. Importantly, favorable treatment outcomes are associated with microbiota alterations that approach those observed in healthy individuals. While the studies reviewed exhibit varying degrees of bias, underscoring the need for further research, this review supports the potential of microbiome modulation as both a preventive and therapeutic strategy for psoriasis patients. The findings underscore the importance of personalized therapeutic approaches, recognizing the profound impact of treatment on the microbiome. They also highlight the promise of probiotics, prebiotics, and dietary interventions in psoriasis management.

CD169+ Skin Macrophages Function as a Specialized Subpopulation in Promoting Psoriasis-like Skin Disease in Mice.

Skin macrophages are critical to maintain and restore skin homeostasis. They serve as major producers of cytokines and chemokines in the skin, participating in diverse biological processes such as wound healing and psoriasis. The heterogeneity and functional diversity of macrophage subpopulations endow them with multifaceted roles in psoriasis development. A distinct subpopulation of skin macrophages, characterized by high expression of CD169, has been reported to exist in both mouse and human skin. However, its role in psoriasis remains unknown. Here, we report that CD169+ macrophages exhibit increased abundance in imiquimod (IMQ) induced psoriasis-like skin lesions. Specific depletion of CD169+ macrophages in CD169-ditheria toxin receptor (CD169-DTR) mice inhibits IMQ-induced psoriasis, resulting in milder symptoms, diminished proinflammatory cytokine levels and reduced proportion of Th17 cells within the skin lesions. Furthermore, transcriptomic analysis uncovers enhanced activity in CD169+ macrophages when compared with CD169- macrophages, characterized by upregulated genes that are associated with cell activation and cell metabolism. Mechanistically, CD169+ macrophages isolated from IMQ-induced skin lesions produce more proinflammatory cytokines and exhibit enhanced ability to promote Th17 cell differentiation in vitro. Collectively, our findings highlight the crucial involvement of CD169+ macrophages in psoriasis development and offer novel insights into the heterogeneity of skin macrophages in the context of psoriasis.

Association between systemic immunity-inflammation index and psoriasis among outpatient US adults.

Background: Psoriasis is a chronic dermatological condition characterized by a complex pathogenesis that impacts approximately 3% of adults in the United States and brings enormous social burdens. For many diseases, the systemic immune-inflammatory index (SII), defined as neutrophils × platelets/lymphocytes, has been recognized as a prognostic indicator. Therefore, we conducted a cross-sectional study to assess the association between SII and psoriasis among outpatient US adults. Methods: In this cross-sectional study, we used data on the US adults 20 to 59 years of age from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2006 and 2009-2014. Sample-weighted logistic regression and stratified analysis of subgroups were used. Results: Among the 16,831 adults, there were 8,801 women and 8,030 men, with a psoriasis prevalence rate of 3.0%. A fully adjusted model revealed a positive association between a SII higher than 479.15 × 109/L and a high risk of psoriasis. According to subgroup analysis and interaction testing (p for interaction > 0.05), age, sex, alcohol drinking status, marital status, and body mass index (BMI) were not significantly correlated with this positive association. Conclusion: Our findings suggested that SII higher than 479.15 × 109/L was positively associated with a high risk of psoriasis among outpatient US adults. To the best of our knowledge, this is the first cross-sectional study using NHANES data focused on the risk of higher SII on psoriasis among outpatient US adults. The outcomes of this cross-sectional serve to supplement previous research, indicating a need for larger-scale prospective cohorts for further validation.

Exploring the pathogenesis and immunological profiles of psoriasis complicated with MASLD.

BACKGROUND: Both psoriasis and metabolic dysfunction-associated steatotic liver disease (MASLD) are immune-mediated chronic inflammatory diseases. Psoriasis manifests itself mainly as skin damage, while MASLD mainly involves the liver promoting liver fibrosis, which has a significant impact on patient health and quality of life. Some clinical studies have shown that there are mutually reinforcing mechanisms between these two diseases, but they are not clearly defined, and this paper aims to further explore their common pathogenesis. METHODS: Gene expression profiling datasets (GSE30999, GSE48452) and single cell datasets (GSE151177, GSE186328) for psoriasis and MASLD were downloaded from the Gene Expression Omnibus (GEO) database. Common differential gene sets were obtained by gene differential analysis, and then functional enrichment of differential genes was performed to find associated transcription factors and PPI protein network analysis. Single-cell datasets were validated for gene expression and explored for cellular communication, gene set differential analysis and immune infiltration analysis. RESULTS: We identified seven common differential genes, all of which were upregulated.The IL-17 pathway, tumor necrosis factor (TNF-α) pathway were shown in strong association with both diseases, and five transcription factors regulating the differential genes were predicted. Two key genes (MMP9, CXCL10) and three key transcription factors (TF) (IRF1, STAT1, NFKB1) were obtained by PPI protein network analysis. Single cell dataset verified the expression of key genes, and combined with gene set differential analysis, immune infiltration revealed that CD4+ T cells, NK cells and macrophages were heavily infiltrated in both diseases. IL-17, IL-1 and cGAS-STING pathways were highly expressed in both diseases, and both diseases share a similar immune microenvironment. CONCLUSIONS: Our study reveals the common pathogenesis of psoriasis and MASLD from gene expression to immune cell similarities and differences, identifies key genes and regulatory pathways common to both, and elucidates the similarities in the immune microenvironment of both diseases, providing new ideas for subsequent studies on targeted therapy.

Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma.

Background: Psoriasis extends beyond its dermatological inflammatory manifestations, encompassing systemic inflammation. Existing studies have indicated a potential risk of cervical cancer among patients with psoriasis, suggesting a potential mechanism of co-morbidity. This study aims to explore the key genes, pathways, and immune cells that may link psoriasis and cervical squamous cell carcinoma (CESC). Methods: The cervical squamous cell carcinoma dataset (GSE63514) was downloaded from the Gene Expression Omnibus (GEO). Two psoriasis-related datasets (GSE13355 and GSE14905) were merged into one comprehensive dataset after removing batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis (WGCNA), and machine learning random forest algorithm (RF) was used to screen the hub genes. We analyzed relevant gene enrichment pathways using GO and KEGG, and immune cell infiltration in psoriasis and CESC samples using CIBERSORT. The miRNA-mRNA and TFs-mRNA regulatory networks were then constructed using Cytoscape, and the biomarkers for psoriasis and CESC were determined. Potential drug targets were obtained from the cMAP database, and biomarker expression levels in hela and psoriatic cell models were quantified by RT-qPCR. Results: In this study, we identified 27 key genes associated with psoriasis and cervical squamous cell carcinoma. NCAPH, UHRF1, CDCA2, CENPN and MELK were identified as hub genes using the Random Forest machine learning algorithm. Chromosome mitotic region segregation, nucleotide binding and DNA methylation are the major enrichment pathways for common DEGs in the mitotic cell cycle. Then we analyzed immune cell infiltration in psoriasis and cervical squamous cell carcinoma samples using CIBERSORT. Meanwhile, we used the cMAP database to identify ten small molecule compounds that interact with the central gene as drug candidates for treatment. By analyzing miRNA-mRNA and TFs-mRNA regulatory networks, we identified three miRNAs and nine transcription factors closely associated with five key genes and validated their expression in external validation datasets and clinical samples. Finally, we examined the diagnostic effects with ROC curves, and performed experimental validation in hela and psoriatic cell models. Conclusions: We identified five biomarkers, NCAPH, UHRF1, CDCA2, CENPN, and MELK, which may play important roles in the common pathogenesis of psoriasis and cervical squamous cell carcinoma, furthermore predict potential therapeutic agents. These findings open up new perspectives for the diagnosis and treatment of psoriasis and squamous cell carcinoma of the cervix.

Associations of novel complete blood count-derived inflammatory markers with psoriasis: a systematic review and meta-analysis.

Psoriasis is an immune-mediated disorder which primarily affects skin and has systemic inflammatory involvement. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte-to-lymphocyte ratio (MLR) are novel complete blood count (CBC)-derived markers which can reflect systemic inflammation. This study aimed to systematically investigate the associations of NLR, PLR, SII, and MLR with psoriasis. This study was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. A comprehensive search of Pubmed, Embase, Scopus, and Google Scholar was conducted for relevant studies. Observational studies evaluating the correlations of NLR, PLR, SII, or MLR with psoriasis were included. The primary outcomes were the associations of these inflammatory markers with the presence and severity of psoriasis. The random-effect model was applied for meta-analysis. 36 studies comprising 4794 psoriasis patients and 55,121 individuals in total were included in the meta-analysis. All inflammatory markers were significantly increased in psoriasis groups compared to healthy controls (NLR: MD = 0.59, 95% CI: 0.47-0.7; PLR: MD = 15.53, 95% CI: 8.48-22.58; SII: MD = 111.58, 95% CI: 61.49-161.68; MLR: MD = 0.034, 95% CI: 0.021-0.048; all p < 0.001). Between-group mean differences in NLR and PLR were positively correlated with the mean scores of Psoriasis Area Severity Index (NLR: p = 0.041; PLR: p = 0.021). NLR, PLR, SII, and MLR are associated with the presence of psoriasis. NLR and PLR serve as significant indicators of psoriasis severity. These novel CBC-derived markers constitute potential targets in the screening and monitoring of psoriasis.

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production.

Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells (DCs) and T cells, ultimately leading to increased production of cytokines such as interleukin (IL)-23 and IL-17A. It is established that the cGAS-STING pathway is essential for psoriatic inflammation, however, the specific role of cGAS-STING signaling in DCs within this context remains unclear. In this study, we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod (IMQ)-treated mice. Using a conditional Sting-knockout transgenic mouse model, we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17- and IFN-γ-producing T cells in psoriatic inflammation. Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells, and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model. Furthermore, we explored the therapeutic potential of the STING inhibitor C-176, which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response. Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.

Role of Ubiquitin-conjugating enzyme E2 (UBE2) in two immune-mediated inflammatory skin diseases: a mendelian randomization analysis.

Psoriasis vulgaris (PV) and Atopic dermatitis (AD) are the two major types of immune-mediated inflammatory skin disease (IMISD). Limited studies reported the association between Ubiquitin-conjugating enzyme E2 (UBE2) and IMISD. We employed a two-sample Mendelian randomization (MR) study to assess the causality between UBE2 and PV & AD. UBE2 association genome-wide association study (GWAS) data were collected. The inverse variance weighted (IVW) method was utilized as the principal method in our Mendelian randomization (MR) study, with additional using the MR-Egger, weighted median, simple mode, and weighted mode methods. The MR-Egger intercept test, Cochran's Q test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy, colocalization analysis was also performed. The results showed that Ubiquitin-conjugating enzyme E2 variant 1 (UBE2V1) was causally associated with PV (OR = 0.909, 95% CI: 0.830-0.996, P = 0.040), Ubiquitin-conjugating enzyme E2 L3 (UBE2L3) was causally associated with AD (OR = 0.799, 95% CI: 0.709-0.990, P < 0.001). Both UBE2V1 and UBE2L3 may play protective roles in patients with PV or AD, respectively. No other significant result has been investigated. No heterogeneity or pleiotropy was observed. This study provided new evidence of the relationship between UBE2V1 and PV, UBE2L3 and AD. Our MR suggested that UBE2V1 plays an inhibitory role in PV progression, UBE2L3 plays an inhibitory role in AD. These could be novel and effective ways to treat PV and AD.

Low rates of vaccination among atopic dermatitis, alopecia areata, psoriasis, and psoriatic arthritis patients on biologics.

Biologics and Janus kinase (JAK) inhibitors are immunomodulating and immunosuppressing medications utilized to treat atopic dermatitis (AD), psoriasis (PSO), psoriatic arthritis (PsA), and alopecia areata (AA). Special recommendations must be considered when prescribing vaccinations in this population, as the pneumococcal and herpes zoster vaccine are recommended to patients ≥ 19-years-old (rather than ≥ 65-years-old and ≥ 50-years-old as in the general population, respectively), along with a yearly influenza and up to date COVID-19 vaccination. Additionally, TNF-α and JAK-inhibitors may increase the risk of latent Hepatitis B virus (HBV) reactivation among high-risk patients. Prior to prescribing these medications, a quantitative HepB Surface Antibody (HepB SA) test is performed to determine immunity. This study utilized the SlicerDicer function on EPIC Medical Records to search for any patient ≥ 19-years-old prescribed a biologic or JAK inhibitor for AD, PSO, PsA, or AA between 10/2003 and 10/2023 at a large tertiary institution. Vaccination rates among patients on biologics and JAK inhibitors were low, with rates being significantly lower in patients 19-64 years-old, compared to those ≥ 65 years-old for most disease states (p < 0.01). Among AD, PSO/PsA, and AA patients, on average, 9.39% were vaccinated for influenza, 6.76% for herpes zoster, 16.56% for pneumococcal pneumonia, and 63.98% for COVID-19. Only 3.16% of patients were adequately vaccinated for HepB after an abnormal HepB SA test. Here, extremely low rates of vaccination among patients on biologics and JAK inhibitors at our institution were highlighted, emphasizing the imperative need for ensuring vaccination in this group.

Orientin alleviates the inflammatory response in psoriasis like dermatitis in BALB/c mice by inhibiting the MAPK signaling pathway.

BACKGROUND: Psoriasis, a chronic inflammatory condition of the skin, is characterized by an atypical proliferation of epidermal keratinocytes and immune cell infiltration. Orientin is a flavonoid monomer with potent anti-inflammatory activities. However, the therapeutic effects of orientin on psoriasis and the underlying mechanisms have not been elucidated. OBJECTIVE: To investigate the therapeutic effect of orientin on psoriasis and the underlying mechanisms using network pharmacology and experimental studies. METHODS: A psoriasis-like mouse model was established using imiquimod (IMQ). Lipopolysaccharide (LPS) was used to stimulate the RAW264.7 and HaCaT cells in vitro. The therapeutic effects of orientin and the underlying mechanism were analyzed using histopathological, immunohistochemical, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, flow cytometry, and western blotting analyses. RESULTS: Orientin ameliorated skin lesions and suppressed keratinocyte proliferation and immune cell infiltration in the IMQ-induced psoriasis-like mouse model. Additionally, orientin inhibited the secretion of the pro-inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-8, IL-17, and IL-23 in the psoriasis-like mouse model and LPS-induced RAW264.7 and HaCaT cells. Furthermore, orientin mitigated the LPS-induced upregulation of reactive oxygen species and downregulation of IL-10 and glutathione levels. Orientin alleviated inflammation by downregulating the MAPK signaling pathway. CONCLUSION: Orientin alleviated psoriasis-like dermatitis by suppressing the MAPK signaling pathway, suggesting that orientin is a potential therapeutic for psoriasis.

Insight into the role of IRF7 in skin and connective tissue diseases.

Interferons (IFNs) are signalling proteins primarily involved in initiating innate immune responses against pathogens and promoting the maturation of immune cells. Interferon Regulatory Factor 7 (IRF7) plays a pivotal role in the IFNs signalling pathway. The activation process of IRF7 is incited by exogenous or abnormal nucleic acids, which is followed by the identification via pattern recognition receptors (PRRs) and the ensuing signalling cascades. Upon activation, IRF7 modulates the expression of both IFNs and inflammatory gene regulation. As a multifunctional transcription factor, IRF7 is mainly expressed in immune cells, yet its presence is also detected in keratinocytes, fibroblasts, and various dermal cell types. In these cells, IRF7 is critical for skin immunity, inflammation, and fibrosis. IRF7 dysregulation may lead to autoimmune and inflammatory skin conditions, including systemic scleroderma (SSc), systemic lupus erythematosus (SLE), Atopic dermatitis (AD) and Psoriasis. This comprehensive review aims to extensively elucidate the role of IRF7 and its signalling pathways in immune cells and keratinocytes, highlighting its significance in skin-related and connective tissue diseases.

Discovery of biomarkers in the psoriasis through machine learning and dynamic immune infiltration in three types of skin lesions.

Introduction: Psoriasis is a chronic skin disease characterized by unique scaling plaques. However, during the acute phase, psoriatic lesions exhibit eczematous changes, making them difficult to distinguish from atopic dermatitis, which poses challenges for the selection of biological agents. This study aimed to identify potential diagnostic genes in psoriatic lesions and investigate their clinical significance. Methods: GSE182740 datasets from the GEO database were analyzed for differential analysis; machine learning algorithms (SVM-RFE and LASSO regression models) are used to screen for diagnostic markers; CIBERSORTx is used to determine the dynamic changes of 22 different immune cell components in normal skin lesions, psoriatic non-lesional skin, and psoriatic lesional skin, as well as the expression of the diagnostic genes in 10 major immune cells, and real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry are used to validate results. Results: We obtained 580 differentially expressed genes (DEGs) in the skin lesion and non-lesion of psoriasis patients, 813 DEGs in mixed patients between non-lesions and lesions, and 96 DEGs in the skin lesion and non-lesion of atopic dermatitis, respectively. Then 144 specific DEGs in psoriasis via a Veen diagram were identified. Ultimately, UGGT1, CCNE1, MMP9 and ARHGEF28 are identified for potential diagnostic genes from these 144 specific DEGs. The value of the selected diagnostic genes was verified by receiver operating characteristic (ROC) curves with expanded samples. The the area under the ROC curve (AUC) exceeded 0.7 for the four diagnosis genes. RT-qPCR results showed that compared to normal human epidermis, the expression of UGGT1, CCNE1, and MMP9 was significantly increased in patients with psoriasis, while ARHGEF28 expression was significantly decreased. Notably, the results of CIBERSORTx showed that CCNE1 was highly expressed in CD4+ T cells and neutrophils, ARHGEF28 was also expressed in mast cells. Additionally, CCNE1 was strongly correlated with IL-17/CXCL8/9/10 and CCL20. Immunohistochemical results showed increased nuclear expression of CCNE1 in psoriatic epidermal cells relative to normal. Conclusion: Based on the performance of the four genes in ROC curves and their expression in immune cells from patients with psoriasis, we suggest that CCNE1 possess higher diagnostic value.