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Background: Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of β2-microglobulin (β2M) in psoriasis severity and comorbidities., Objectives: To investigate the correlation between blood β2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension., Methods: Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks., Results: Significantly higher levels of blood β2M and ESR were observed in the group that patients' PASI ≥10 than in the group that PASI <10. Blood β2M level had strong significantly positive correlations with the PASI in Pearson's correlation analysis. In the model that systemic inflammatory factors to find psoriasis comorbidity risk factors, logistic regression analysis showed that blood β2M level was the significant risk factor associated with diabetes and hypertension. High-sensitivity C-reactive protein (hsCRP) was the significant risk factor associated with arthritis., Conclusions: Patients with a severer psoriasis tended to have higher blood β2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood β2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis.

Objective: Methotrexate (MTX) is an economic and effective medicine treatment for psoriasis. Extracellular vesicle (EV) miRNA biomarkers related to its efficiency have been identified in various diseases. Whether certain miRNA profiles are associated with psoriasis treatment is unknown. In order to determine specific miRNA biomarkers for MTX effectiveness prediction and the severity of psoriasis, our study looked at the variations in circulating EV miRNA profiles before and after MTX therapy., Methods: Plasma EV isolation and next-generation sequencing were performed to identify differentially expressed EV miRNAs between GRs (n = 14) and NRs (n = 6). Univariate and multiple linear regression analyses were performed to evaluate the correlation between PASI scores and miRNA expression levels., Results: 15 miRNAs out of a total profile of 443 miRNAs were substantially different between GRs and NRs at baseline, 4 of them (miR-199a-5p, miR-195-5p, miR-196a-5p, and miR-1246) have the potential to distinguish between GRs and NRs [area under the curve (AUC) ≥ 0.70, all P < 0.05]. KEGG pathway analyses revealed differentially expressed miRNAs to potentially target immune-related pathways. SIRT1 was discovered to be a target of miR-199a-5p and involved in MAPK signaling pathway. MiR-191-5p and miR-21-5p expression levels have been discovered to positively correlate with PASI scores[P < 0.05]., Conclusion: This pilot investigation found that miR-199a-5p, miR-195-5p, miR-196a-5p, and miR-1246 might be prospective biomarkers to predict the efficacy of MTX, and that miR-191-5p and miR-21-5p were correlated with psoriasis severity. Five of them previously reported to be involved in MAPK signaling pathway, indicating a potential role of MTX in delaying the progression of psoriatic inflammation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

B7-H4 is a recently discovered member of B7 family that negatively regulates T-cell immunity, specifically Th1 and Th17 cell responses. However, its role in the pathogenesis of psoriasis has yet to be determined. This study aims to investigate the effect of B7-H4 polymorphism on the efficacy of methotrexate (MTX) and its mechanism in psoriasis. Four single nucleotide polymorphisms of B7-H4 were genotyped in 310 psoriatic patients who received 12-week MTX. The protein expression of B7-H4 in platelets was characterized using immunofluorescence staining, confocal laser scanning microscopy, and flow cytometry techniques. We found that GG genotype carriers of B7-H4 rs1935780 had a lower Psoriasis Area and Severity Index (PASI) 75 response rate and higher weight (p = 0.0245) and body mass index (p = 0.0185) than AA and AG genotype carriers. Multiple regression analysis showed that the PASI score at baseline (p = 0.01) and age at disease onset (p = 0.003) were positively correlated with PASI 75 response rate, while weight (p = 0.005) and the rs1935780 genotype (p = 0.003) were negatively associated with PASI 75 response rate. B7-H4 was expressed in the platelet plasma membrane and cytoplasm. Furthermore, the expression of B7-H4 protein in platelets was lower in good responders than in non-responders and was upregulated considerably after 12-week MTX or in vitro MTX stimulation in good responders. Collectively, these results demonstrate that psoriatic patients with GG genotype of B7-H4 rs1935780 had a poorer response to MTX. Low expression of B7-H4 protein in platelets correlated with better clinical outcomes of MTX in psoriasis., (© 2023 John Wiley & Sons Ltd.)

Background: The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of methotrexate (MTX) in psoriasis patients., Methods: Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single-nucleotide polymorphisms in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by Western blot., Results: Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among the three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend., Conclusion: By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response., (© 2023 S. Karger AG, Basel.)

Background: Psoriasis is an inflammatory disease mediated by helper T (Th)17 and Th1 cells. MicroRNA-125a (miR-125a) is reduced in the lesional skin of psoriatic patients. However, the mechanism by which miR-125a participates in psoriasis remains unclear., Methods: The levels of miR-125a-5p and its downstream targets (ETS-1, IFN-γ, and STAT3) were detected in CD4 + T cells of healthy controls and psoriatic patients by quantitative real-time PCR (qRT-PCR). In vitro, transfection of miR-125a-5p mimics was used to analyze the effect of miR-125a-5p on the differentiation of Th17 cells by flow cytometry. Imiquimod (IMQ)-induced mouse model was used to evaluate the role of upregulating miR-125a-5p by intradermal injection of agomir-125a-5p in vivo., Results: miR-125a-5p was downregulated in peripheral blood CD4 + T cells of psoriatic patients, which was positively associated with the proportion of regulatory T cells (Tregs) and negatively correlated with the Psoriasis Area and Severity Index (PASI) score. Moreover, the miR-125a-5p mimics promoted the differentiation of Tregs and downregulated the messenger RNA (mRNA) levels of ETS-1, IFN-γ, and STAT3 in murine CD4 + T cells. Furthermore, agomir-125a-5p alleviated psoriasis-like inflammation in an IMQ-induced mouse model by downregulating the proportion of Th17 cells., Conclusions: miR-125a-5p may have therapeutic potential in psoriasis by restoring the suppressive function of Tregs on Th17 cells through targeting STAT3, and on Th1 cells indirectly through targeting ETS-1 and IFN-γ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The mevalonate-diphosphate decarboxylase (MVD) gene, a member of the mevalonate pathway, plays a critical role in regulating the biosynthesis of cholesterol, steroid hormones, and non-steroid isoprenoids. Previous studies have suggested that the MVD c.746 T > C mutation is a major pathogenic gene of porokeratosis (PK), an autoinflammatory keratinization disease (AIKD) with unclear pathogenesis, few effective treatments, and no suitable animal model. To investigate the function of Mvd F250S/+ mutation, we developed a novel Mvd F250S/+ mouse model carrying an equivalent point mutation to the most common genetic variation among Chinese PK patients (MVD F249S/+ ) using CRISPR/Cas9 technology, which exhibited reduced cutaneous expression of Mvd protein. In the absence of external stimulation, Mvd F250S/+ mice did not display specific phenotypes. However, upon induction with imiquimod (IMQ), Mvd F250S/+ mice exhibited decreased susceptibility to skin acute inflammation compared to wild-type (WT) mice, as evidenced by reduced cutaneous proliferation and lower protein levels of IL-17a and IL-1β. Additionally, after IMQ induction, the Mvd F250S/+ mice exhibited downregulated collagen generation and upregulated expression of Fabp3 compared to WT mice, whereas no significant changes in the key genes related to cholesterol regulation were found. Furthermore, the Mvd F250S/+ mutation activated autophagy. Our findings provided insights into the biological function of MVD in the skin., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

MTX in genetically distinctive Chinese psoriatic patients remains less explored. The present study aimed to determine the impact of HLA-Cw*06 on MTX response in a Chinese psoriasis patient population. A total of 204 patients with psoriasis were enrolled in this study. Clinical data and DNA samples from all patients were collected. The allele of HLA-Cw*06 genotyping was detected using direct Sanger sequencing. This study enrolled 204 patients with psoriasis, including 47 (23.04%) psoriatic arthritis patients, 157 (76.96%) patients free of psoriatic arthritis. Overall, 110 (53.92%) of all patients carried the HLA-Cw*06 allele. This frequency in patients with arthritis-free psoriasis was higher than that in those with psoriatic arthritis (58.59 vs. 38.30%, P = 0.014). After 8 weeks of MTX treatment, the arthritis-free psoriasis patients, who tested positive for the HLA-Cw*06 allele, showed significant improvement compared to those who tested negative (For PASI50, 78.57 vs. 55.22%, P = 0.02, and for PASI75, 51.11 vs. 34.33%, P = 0.036). The psoriatic arthritis-free patients who carried the HLA-Cw*06 allele in combination with the ABCB1 rs1045642 CC genotype showed the highest improvement. A regression model containing HLA-Cw*06, rs1045642T > C, and initial PASI scores was used to construct the efficacy prediction model of MTX, which yielded AUC values of 73.2 and 75.6% for PASI50 and PASI75 to MTX, respectively, in arthritis-free psoriasis patients. The HLA-Cw*06 allele is associated with optimal response to MTX treatment in arthritis-free Chinese psoriasis patients. When combined with clinical indicators, the polymorphism explained more than 75% of the individual efficacy differences., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis., Methods: Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists., Results: A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%)., Conclusion: The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14 + cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.

Background: Methotrexate (MTX) is the first-line medicine to treat psoriasis. So far, there has been less research on protein biomarkers to predict its efficacy by the proteomic technique., Objectives: To evaluate differentially expressed proteins in peripheral mononuclear cells (PBMCs) between good responders (GRs) and non-responders (NRs) after MTX treatment, compared with normal controls (NCs)., Methods: We quantified protein expression of PBMCs with four GRs and four NRs to MTX and four NCs by isobaric tags for relative and absolute quantification (iTRAQ), analysing and identifying proteins related to efficacy of MTX in 18 psoriatic patients., Results: A total of 3177 proteins had quantitative information, and 403 differentially expressed proteins (fold change ≥1.2, P < 0.05) were identified. Compared to NCs, upregulated proteins (ANXA6, RPS27A, EZR, XRCC6), participating in the activation of NF-κB, the JAK-STAT pathway and neutrophil degranulation were detected in GRs. The proteins (GPV, FN1, STOM), involving platelet activation, signalling and aggregation as well as neutrophil degranulation were significantly downregulated in GRs. These proteins returned to normal levels after MTX treatment. Furthermore, Western blotting identified the expression of ANXA6 and STAT1 in PBMCs, which were significantly downregulated in GRs, but not in NRs., Conclusions: We identified seven differentially expressed and regulated proteins (ANXA6, GPV, FN1, XRCC6, STOM, RPS27A and EZR) as biomarkers to predict MTX efficacy in NF-κB signalling, JAK-STAT pathways, neutrophil degranulation, platelet activation, signalling and aggregation., (© 2022 European Academy of Dermatology and Venereology.)

Background: Vunakizumab (SHR-1314) is a novel interleukin 17A monoclonal antibody that has shown preliminary efficacy and tolerability in phase I trials., Objective: To evaluate the efficacy and safety of vunakizumab in moderate-to-severe plaque psoriasis., Methods: In this 36-week, multicenter, double-blinded, phase II study (NCT03463187), 187 eligible patients with moderate-to-severe plaque psoriasis were randomized 1:1:1:1:1 to receive vunakizumab (40, 80, 160, or 240 mg) or placebo subcutaneously, every 4 weeks, until week 12 (2 more drug administrations for the vunakizumab groups on weeks 16 and 20). The primary end point was at least 75% improvement in the Psoriasis Area and Severity Index at week 12., Results: At week 12, there were significantly greater proportions of responders with at least 75% improvement in the Psoriasis Area and Severity Index in all vunakizumab groups compared to placebo (40, 80, 160, and 240 mg: 56.8%, 65.8%, 81.6%, and 86.5%, respectively, vs 5.4%; P < .001 for all); the proportions of patients achieving Physician's Global Assessment responses of 0 or 1 were also higher with vunakizumab (45.9%, 47.4%, 60.5%, and 73.0%, respectively, vs 8.1%). No unexpected adverse effects were observed., Limitations: The study was relatively short in duration and included no active control., Conclusion: Vunakizumab showed promising efficacy for moderate-to-severe plaque psoriasis, with good tolerability, warranting further investigation in larger and longer-term studies., Competing Interests: Conflicts of interest Dr Sinclair is the director and founder of Samson Medical Pty Ltd, serves on the advisory boards of Eli Lilly and Company, Pfizer Inc, and Leo Pharmaceutical, and has been a speaker for Abbvie and Novartis and a principal investigator in clinical trials for AbbVie, Aerotech, Akesobio, Amgen, Arcutis, Arena, Ascend AstraZeneca, Bayer AG, Biotherapeutics Boehringer Ingelheim, Bristol Myer Squibb, Celgene, Coherus BioSciences, Connect, Demira, Eli Lilly and Company, Galderma, Glaxo Smith Kline, F. Hoffman–La Roche, Janssen, MedImmune, Merck and Co, Merck Sharpe & Dohme, Novartis, Oncobiologics, Pfizer, Principia, Regeneron, Roche, Reistone Biopharma, Samson Clinical, Sanofi-Genzyme, and Sun Pharma UCB. Author Zhu and Dr Qian Xu were employees of Hengrui Pharmaceuticals at the time of the study. Drs Zhang, Yan, Diao, Guo, Jin, Yang, Chen, Lei, Wu, Yu, Zheng, Gao, and Jinhua Xu have no conflicts of interest to declare., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Psoriasis is a chronic, immune-mediated inflammatory disease which pathogenesis is closely linked to γδ T cells. Recently, a critical role for butyrophilin 3A1 (BTN3A1) in mediating the activation of Vγ9Vδ2 T cells, which are reported to redistribute from blood to the perturbed skin lesions in psoriasis, has been proposed. Additional molecular partners, including RhoB and periplakin, have also been speculated to interact with BTN3A1 in modulating Vγ9Vδ2 T-cell activation. Immunohistochemical staining was performed to examine the expressions of BTN3A1, RhoB, and the plakin family members, including periplakin, epiplakin, and envoplakin in the psoriasis vulgaris lesions as compared with the normal control. The expressions of BTN3A1 and RhoB were found significantly upregulated in the psoriatic lesions. Besides, a downregulation of periplakin and an upregulation of epiplakin were noticed in the psoriasis vulgaris lesions. Our data suggest that BTN3A1 and RhoB might participate in the pathogenesis of psoriasis through Vγ9Vδ2 T-cell responses. In addition, a potential involvement of the plakin protein family, especially periplakin and epiplakin, in psoriasis pathology was proposed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear., Objective: To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA)., Methods: In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured., Results: Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients., Conclusion: PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex., Trial Registration: ChiCTR2000036192., (© 2022. The Author(s).)

Background: Psoriasis is associated with an increased risk for cardiovascular disease (CVD). Methotrexate (MTX) is often used as a first-line system therapy and there is a need to determine its effect on whole blood viscosity (WBV) and plasma viscosity (PV) in psoriasis.METHODSA prospective, single-center, interventional study with a total of 111 psoriatic patients who received MTX therapy from October 22, 2018, to December 28, 2019, and 111 age- and sex-matched healthy controls. Changes in WBV, PV, blood counts, liver and renal function were evaluated.RESULTSPsoriatic patients had significantly higher levels of WBV and relative viscosity (RV) at low shear rate (LSR), erythrocyte aggregation index (EAI), and PV than sex and age-matched healthy controls. PV was positively correlated with erythrocyte sedimentation rate (ESR), ESR was positively correlated with high sensitive C-reactive protein (hCRP). But only hCRP was positively associated with psoriasis area severity index (PASI) score. MTX significantly decreased the levels of PV, ESR, hCRP, and blood pressure (BP) in male patients, and the level of WBV in female patients., Conclusion: Sex-specific downregulation of MTX on WBV, PV, hCRP, and BP, indicating that the effect of MTX on the risk of cardiovascular disease was related with sex.

Background: Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking., Methods: We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC-MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins., Results: We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p < 0.05) in the comparison of all psoriatic patients versus healthy controls, PsO group versus healthy controls, PsA group versus healthy controls, and PsA group versus PsO group, respectively. Among these proteins, 14 proteins may represent promising biomarkers for PsA: SIRT2, NAA50, ARF6, ADPRHL2, SF3B6, SH3KBP1, UBA3, SCP2, RPS5, NUDT5, NCBP1, SYNE1, NDUFB7, HTATSF1. Furthermore, western blotting confirmed that SIRT2 expression was significantly higher in PBMCs from PsA patients than PsO and healthy controls, and was negatively correlated with the phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK; p = 0.006, r = - 0.582)., Conclusions: This pilot study provided a broad characterization of the proteome of PBMCs in PsA as compared to PsO and healthy controls, which may help to provide prospective strategies for PsA diagnosis., (© 2021. The Author(s).)

Background: The anti-inflammatory effect of glycyrrhizin has been widely recognized, while the specific mechanism of glycyrrhizin in psoriasis remains poorly understood., Results: In the imiquimod-induced mouse model of psoriasis (IMD), we found that glycyrrhizin can substantially improve the adverse symptoms in mice. The hematoxylin-eosin staining results showed that glycyrrhizin can also improve the pathological state of skin cells in IMD mice. Using enzyme-linked immunosorbent assay (ELISA), we found that glycyrrhizin substantially inhibited the expression of IL-17A and IFN-γ in the serum of IMD mice. In order to simulate the effect of IL-17A on keratinocytes in psoriasis, we treated HaCaT cells with 100 ng/mL IL-17A (IL-17A-HaCaT cells) for 48 h. Then, using cell-counting kit-8 (CCK-8) and ELISA assays, we found that glycyrrhizin inhibited the proliferation of IL-17A-HaCaT cells and reversed the promotion of IL-6, CCL20, and TNF-α induced by IL-17A. Further, western blotting (WB) results indicated that glycyrrhizin promoted the expression of SIRT1 and inhibited the expression of STAT3 and phosphorylated STAT3 (p-STAT3). By treating IL-17A-HaCaT cells with EX-527 (a potent and selective inhibitor of SIRT1), combined with CCK-8 and WB experiments, we initially found that EX-527 inhibited the proliferation of IL-17A-HaCaT cells and promoted the expression of STAT3, p-STAT3, and acetylated STAT3 (a-STAT3). However, when glycyrrhizin was added at the same time, the proliferation of IL-17A-HaCaT cells increased, and the expression of STAT3, p-STAT3, and a-STAT3 reduced. We then knocked down the expression of SIRT1 via small interfering RNA in IL-17A-HaCaT cells, and the results were consistent with those of EX-527., Conclusions: Together, these results indicated that glycyrrhizin improved psoriasis by inhibiting the expression of IL-17A and IFN-γ in vivo and suppressed the proliferation of IL-17A-HaCaT cells and the expression of STAT3, p-STAT3, and a-STAT3 by upregulating SIRT1 in vitro.

Background: There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients' genetic background seems promising in its explanation., Objectives: The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy., Methods: A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI <50%) compared to baseline after 12 weeks of short-time therapy. On 1-year treatment, they were defined as responders if they achieved PASI75 and absolute PASI ≤3, otherwise as nonresponders. The genotypes of 4 single-nucleotide polymorphisms (SNPs) in the ANxA6 gene were verified using the Sequenom platform. Potential predictors associated with the treatment outcome of MTX were assessed by binary logistic regression., Results: We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (p = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245-0.951, p = 0.035; at 1 year: OR 0.483, 95% CI 0.280-0.833, p = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (p = 0.018 and p = 0.036, respectively)., Conclusions: The CC ge-notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX., (© 2021 S. Karger AG, Basel.)

Background: Methotrexate (MTX) is the first-line treatment for psoriasis in China. The metabolic processes of MTX include various proteins and genes. Previous studies have shown that gene polymorphisms had significant impacts on the efficacy of MTX. However, the influence of gene polymorphisms has not been reported in the Chinese psoriatic patients., Objective: The aim of this study was to verify the impacts of candidate genes polymorphisms on the effectiveness of MTX in a Chinese psoriatic population., Methods: In this study, we enrolled 259 psoriasis patients from two clinical centres. Each of them received MTX treatment at 7.5-15 mg/week for at least 8 weeks. Patients were stratified as responders and non-responders according to whether the Psoriasis Area and Severity Index score declined more than 75% (PASI75). According to previous reports, 16 single nucleotide polymorphisms (SNPs) were selected and genotyped for each patient using the Sequenom platform. Fisher's exact test, the chi-square test, Mann-Whitney tests and ANOVA analyses were used for statistical analysis., Results: Among 259 patients, there were 182 males and 77 females, 63 patients with psoriatic arthritis and 196 patients without arthritis phenotype, and the age of all patients ranged from 19 to 70 years (49.7 ± 13.6). The baseline PASI value of patients was 13.8 ± 8.5, and 33.2% of patients achieved a PASI75 response after MTX treatment. Patients carrying the ATP-binding cassette subfamily B member 1 gene (ABCB1) rs1045642 TT genotype were associated with more severe psoriasis skin lesion (P = 0.032). Furthermore, the ABCB1 rs1045642 TT genotype was found to be more frequent in non-responders (P = 0.017), especially in moderate-to-severe patients (P = 0.002) and patients without psoriatic arthritis (P = 0.026) after MTX treatment., Conclusion: We have demonstrated for the first time that polymorphism of the ABCB1 rs1045642 TT genotype is predictive of a worse clinical response of skin lesions to MTX therapy in a Chinese psoriatic population., (© 2020 European Academy of Dermatology and Venereology.)

Psoriasis-2 (PSORS2) is caused by the heterozygous mutation of the caspase recruitment domain 14 ( CARD14 ) gene on chromosome 17q25. To evaluate the contribution of CARD14 variants in psoriasis of the Chinese Han population, we performed deep sequencing of the CARD14 gene in 372 Chinese Han patients with psoriasis. The exonic nucleotide variants were confirmed by Sanger sequencing in the affected individuals and 1114 controls. In 27 patients with psoriasis, we identified 15 variations, including three novel variants: c.381C[G (p.Cys127Trp), c.712A[G (p.Met238Val) and c.2260&#95;2261delinsGG (p.Gln754Gly). These findings could enrich and update the Human Gene Mutation Database of CARD14 variants for psoriasis.

Background: Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy., Objectives: To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort., Methods: A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single-nucleotide polymorphisms in 14 susceptibility genes, and HLA-Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients., Results: Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI (P < 0·05), arthritis (P < 0·05) and genotype of rs10036748 (P < 0·05) were significantly associated with clinical responses to MTX., Conclusions: Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX., (© 2019 British Association of Dermatologists.)

The prevalence of psoriasis is increasing, and poses a serious risk to human health and quality of life. Psoriasis, a chronic immune‑mediated skin disease with epidermal hyperkeratosis and parakeratosis, is associated with numerous complications, including metabolic syndromes that are regulated by sirtuins (SIRTs) via deacetylation. As they serve a necessary function in inflammation and metabolism, SIRTs are considered to link inflammation and metabolic syndrome. Previous studies have indicated that SIRTs serve a function in the pathophysiology of psoriasis, but to date no detailed research has been conducted investigating the expression levels and patterns of SIRTs in psoriasis. The present study investigated the abnormal expression of SIRTs in psoriasis and provided a theoretical foundation for the treatment and prognosis of psoriasis. Tumor necrosis factor (TNF)‑α‑stimulated HaCaT cells and an imiquimod‑induced psoriasis mouse model were used to produce in vitro and in vivo models, respectively. Psoriasis clinical specimens (psoriasis area and severity index >10; n=22) and normal group specimens (n=22) were obtained from human subjects. The mRNA and protein expression levels in human and mouse skin lesions and TNF‑α‑stimulated HaCaT cells were detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting, and compared with the control groups. The expression patterns of SIRT proteins were investigated using immunofluorescence (IF) staining. The expression levels of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 were downregulated while those of SIRT6 and SIRT7 were upregulated in skin lesions and TNF‑α‑stimulated HaCaT cells compared with the control group as determined by RT‑qPCR, western blotting and IF. Statistically significant differences were observed in vivo and in vitro. P‑values of SIRT1‑7 mRNA are less than 0.05 in RT‑qPCR, and the P‑values of SIRT1‑7 proteins are less than 0.05 except for SIRT4 in the western blot analysis. SIRTs serve notable functions in severe psoriasis dermatitis, with the overexpression of SIRT6 and SIRT7 potentially induced by the adaptive immune response, and the downregulation of SIRT1, SIRT2, SIRT3, SIRT4 and SIRT5 may be a result of an internal environment imbalance in vivo. Psoriasis is an inflammation and metabolism‑associated disease mediated by the SIRT family. The present results provide a novel potential mechanism and strategy for the treatment of psoriasis by modulating the function and expression of SIRTs.

Previous studies have reported a higher incidence of depression and anxiety in psoriasis patients compared to the general population, which has important implications for assessment and treatment. In this study, we determined the frequency of depression and anxiety in Chinese patients with psoriasis and its relationship with disease severity and other demographic variables. The study included 208 Chinese patients with psoriasis vulgaris. The Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7) were used to screen for depression and anxiety. The Psoriasis Area and Severity Index (PASI) was used to assess the severity of psoriasis. Of the 208 patients included in the study, 29 patients (13.9%) were positive for moderate-to-severe depression (PHQ-9 ≥ 10) and 22 patients (10.6%) were positive for anxiety (GAD-7 ≥ 10) symptoms. Both positive stress reactors who perceived stress as an exacerbating factor of psoriasis and moderate-to-severe psoriasis were found to be positive predictors for the presence of moderate-to-severe depression or anxiety symptoms while longer duration and late onset age played a protective role. In the sample of Chinese patients with psoriasis there was a clinically significant prevalence of depression and anxiety. Our study suggests that Chinese psoriasis patients should be screened for psychiatric comorbidities.

Importance: It is necessary to determine whether psoriasis responds to methotrexate in the same manner in patients with and without psoriatic arthritis., Objective: To evaluate the effectiveness and safety of methotrexate in treating patients with psoriasis with and without psoriatic arthritis., Design, Setting, and Participants: In this prospective, single-arm, interventional study, a total of 235 patients with psoriasis, 107 without psoriatic arthritis and 128 with psoriatic arthritis who were receiving methotrexate therapy from April 1, 2015, to December 31, 2017, were recruited from the outpatient department of a hospital at a large Chinese university. There were no significant demographic or clinical differences between the subgroups with the exception of diabetes., Interventions: A 12-week course of low-dosage oral methotrexate (7.5-15 mg weekly)., Main Outcomes and Measures: Changes in disease severity, adverse events, blood cell counts, and liver and renal function., Results: A total of 235 patients with psoriasis (166 male [66.0%]; mean [SD] age, 49.6 [15.1] years) received methotrexate treatment for 12 weeks. The 90% reduction from baseline Psoriasis Area Severity Index response was significantly lower in patients with psoriatic arthritis than in patients without psoriatic arthritis at week 8 (4 0f 128 [3.1%] vs 12 of 107 [11.2%]; P = .02) and week 12 (19 of 128 [14.8%] vs 27 of 107 [25.2%]; P = .049). Furthermore, the incidence of adverse events, including dizziness (12 of 128 [9.4%] vs 1 of 107 [0.9%]; P = .007), gastrointestinal symptoms (32 of 128 [25.0%] vs 13 of 107 [12.1%]; P = .01), and hepatoxicity (34 of 128 [26.6%] vs 16 of 107 [15.0%]; P = .04), was significantly higher in patients with psoriatic arthritis than in patients without psoriatic arthritis. Methotrexate-induced elevation of alanine aminotransferase levels was associated with body mass index (mean [SD] body mass index, 26 [4] in patients with [P = .04] vs 26 [4] in those without [P = .005] psoriatic arthritis) and smoking (17 of 34 [50.0%] in patients with [P = .02] vs 9 of 16 [56.3%] in those without [P = .04] psoriatic arthritis)., Conclusions and Relevance: In this study, methotrexate was well tolerated and effective in treating psoriasis. It was more effective, with fewer adverse effects, in patients with psoriasis who did not have psoriatic arthritis than in patients who presented with both psoriasis and psoriatic arthritis. Therefore, methotrexate can be recommended as first-line treatment for psoriasis without arthritis.

Background: Few studies have explored the differences of immunopathogenesis in plaque vs guttate psoriasis, especially on the inhibitory role of regulatory T cells (Tregs) on IL-17/ IFN-γ production and the impact of CD4+T cells on keratinocytes., Objective: To investigate the percentage and inhibitory function of CD4+CD25 high Treg and differential expressions of IL-17/ IFN-γ in plaque vs guttate psoriasis, and the effects of CD4+T cells on the proliferation of keratinocytes., Methods: Peripheral blood mononuclear cells (PBMCs) were prepared from patients with the plaque and guttate psoriasis. The percentage of CD4+CD25 high Tregs, IL-17/IFN-γ- producing CD4+ or CD8+T cells, and apoptosis and cell cycle of Hacat cells were determined by flow cytometry. The level of IFN-γ in supernatants was analyzed by ELISA., Results: The percentage of CD4+CD25 high Tregs in plaque psoriasis was significantly increased, and they can inhibit IFN-γ production from CD4+CD25- effector T cells. The percentage of CD8+IFN-γ+cells was also significantly increased in plaque psoriasis, and these cells positively correlated with disease severity. The percentage of CD4+CD25 high Tregs was decreased and CD4+IFN-γ+/IFN-γ+IL-17+ cells were predominantly increased in guttate psoriasis. CD4+T cells from guttate psoriasis induce apoptosis of keratinocytes while they promote the proliferation of keratinocytes in plaque psoriasis by decreasing late apoptosis and increasing the percentage of G1 phase., Conclusion: There was considerable discrepancy of the phenotype and function of T cells between plaque vs guttate psoriasis. IFN-γ and IL-17 from CD4+T cells play a crucial role in guttate psoriasis, however, IFN-γ and IL-17 from CD8+T cells are more important in the immunopathogenesis of plaque psoriasis., (Copyright © 2018. Published by Elsevier B.V.)

Background: Methotrexate (MTX) is used to treat psoriasis, a chronic inflammatory skin disease., Objectives: To investigate the molecular mechanism of MTX in the treatment of psoriasis., Methods: Regulatory T cells (Tregs) and effector T (Teff) cells were isolated from the blood of patients with psoriasis and healthy controls. The proliferation of Teff cells was detected by carboxyfluorescein succinimidyl ester assay. The interferon (IFN)-γ and interleukin (IL)-17 levels were analysed by enzyme-linked immunosorbent assay. The expression of CD73 and FoxP3 were determined by flow cytometry. The expression of proteins in the AMPK/mTOR pathway were detected by Western blot analysis., Results: The data suggested that patients with psoriasis have Tregs with decreased immune suppression function and reduced expression of CD73 compared with healthy controls. Moreover, MTX could significantly restore the immunosuppressive function of IL-17-secreting Tregs. This, in turn, inhibits aberrant proliferation of Teff cells in patients with psoriasis, reverses downregulation of CD73, upregulates phosphorylated AMPK and inhibits phosphorylated mTOR, and downregulates IL-17 and IFN-γ levels., Conclusions: We speculate that MTX can restore the immunosuppressive function of Tregs through upregulating CD73, activating AMPK and inactivating the mTOR pathway. These findings may partly explain the mechanism by which MTX treats psoriasis., (© 2018 British Association of Dermatologists.)

Background: CD39 and CD73 are two novel cell surface markers of CD25 high Foxp3 + regulatory T-cells (Tregs). Concordant expression of these two ectoenzymes not only discriminate Tregs from other cell populations, but also generates pericellular adenosine, which has been reported to suppress proliferation of activated T effector (Teff) cells. Because it is currently unclear whether human ectoenzymes (CD39/CD73) are involved in the impaired suppressive activity of Tregs in psoriasis, we examined the frequencies and phenotypes of CD39/CD73-expressing Tregs and related receptor adenosine receptor 2A (A 2A R) in peripheral blood of patients with different types of psoriasis., Methods: Peripheral blood mononuclear cells (PMBC) were prepared from patients with three different types of psoriasis (psoriasis vulgaris, pustular psoriasis and erythrodermic psoriasis). CD4 + cells were separated from PBMC by negative selection on midiMACS columns, and the frequencies and phenotypes of CD39 and CD73 expressing Tregs, and A 2A R expressing Teff were all determined by flow cytometry analysis. Blood from healthy volunteers served as controls., Results: The expression of single CD73 + Tregs was markedly reduced (approximately 50%) in psoriasis vulgaris, compared to normal controls. In pustular psoriasis, the mean numbers of CD39 + Tregs and A 2A R + Teff was significantly lower than in normal controls. Among three different types of psoriasis, CD39 expression was strikingly reduced in the blood Treg population of pustular psoriasis patients. Decreased CD73 + Tregs levels were observed in psoriasis vulgaris compared to pustular psoriasis and erythrodermic psoriasis., Conclusions: The differences in the expression of CD39 - and CD73 - Tregs may be a factor in the pathogenesis of psoriasis., (© 2017 The Authors. Australasian Journal of Dermatology published by Wiley Publishing Asia Pty Ltd on behalf of The Australasian College of Dermatologists.)

Background: Although elevated serum IgE levels have been reported in psoriasis, the role of IgE in psoriasis still needs to be clarified., Objectives: To analyse serum total IgE levels in addition to the presence and distribution of IgE and FcεRI in psoriatic lesions, and to investigate alteration of IgE and FcεRI after successful systemic treatment., Methods: Total serum IgE levels were determined using enzyme-linked immunosorbent assay. The expression and localization of IgE and FcεRI was investigated using immunohistochemistry and double immunofluorescence., Results: Elevated total serum IgE levels were found in 39% of patients with psoriasis. The levels of total serum IgE were significantly higher in male patients compared with female patients. Furthermore, total serum IgE levels decreased after successful systemic treatment. A positive correlation between IgE+ and FcεRI+ cells and a significant increase of these cells was found in psoriatic lesions when compared with normal skin. Interestingly, IgE+ and FcεRI+ cells decreased significantly after successful therapy with ustekinumab. IgE and FcεRI were coexpressed on mast cells, epidermal Langerhans cells, dermal dendritic cells, macrophages and a small number of neutrophils., Conclusions: IgE might participate in the development of psoriasis by activating FcεRI-bearing cells., (© 2016 British Association of Dermatologists.)

Background: Psoriasis is a chronic, relapsing, inflammatory skin disease, in which regulatory T cells (Tregs) play an important role. Recently, human Treg ectoenzymes (CD39/CD73) have been reported to mediate the suppressive activity of Tregs., Aim: To investigate the proportions of CD39/CD73 expressing Foxp3(+) regulatory T cells in different types of psoriatic lesions., Methods: Immunohistochemical staining was used to analyse expression of Foxp3, CD39 and CD73 in biopsy tissue from healthy controls and from patients with different types of psoriasis., Results: In normal control biopsies, CD39(+) cells were scattered throughout the epidermis and dermis, while CD73(+) cells were localized predominantly in the dermis. The proportion of cells that were both CD39(+) and Foxp3(+) was significantly lower in pustular psoriasis (PP) and erythrodermic psoriasis (EP) than in psoriasis vulgaris (PV) (25.0 ± 2.6%, 26.5 ± 2.0% and 45.1 ± 3.5%, respectively; P < 0.001). Likewise, CD73(+) Foxp3(+) cells were lower in PP and EP than in PV (6.2 ± 1.9%, 11.6 ± 2.8% and 17.7 ± 2.3% respectively, P < 0.001). There were no significant differences in the population size of double-staining cells in EP compared with PP., Conclusion: The relative reduced expressions of CD39 and CD73 within Foxp3(+) Tregs may imply a different immunopathogenesis for different psoriatic lesions., (© 2014 British Association of Dermatologists.)

Background: Differences in the number of Foxp3+ regulatory T cells (Tregs) in lesional skin and peripheral blood and their functioning in plaque vs. guttate psoriasis have not been reported., Objectives: To investigate whether there is a differential expression of Foxp3+ Tregs and a differential regulation of inflammatory cytokines in plaque vs. guttate psoriasis vulgaris., Methods: The number and the percentage of Foxp3+ cells in different phases of skin lesions of patients with plaque and guttate psoriasis vulgaris were assessed by immunohistochemical staining. The expression of Foxp3 and interleukin (IL)-17 protein in CD4 populations was measured by flow cytometry. Inflammatory cytokine production by transforming growth factor-beta1-induced Foxp3+ Tregs was assessed in an in vitro study. The cytokines in supernatant and serum were determined by enzyme-linked immunosorbent assay., Results: The percentage of Foxp3+ CD3+ cells in the papillary layer was higher than in the reticular layer of dermis and in epidermis (P < 0.05). The numbers of Foxp3+ Tregs in skin lesions and peripheral blood were higher in plaque than in guttate psoriasis, whereas the percentage of IL-17+ CD4+ cells was higher in guttate than in plaque psoriasis (P < 0.05). The numbers of Foxp3+ cells were positively correlated with the Psoriasis Severity Index score of skin lesions (P < 0.0001), and the percentages of Foxp3+ CD4+ cells in peripheral blood were positively correlated with the Psoriasis Area and Severity Index score of patients (P < 0.05). The inhibitory functions of Tregs to IL-17 and IL-6 in guttate psoriasis and to tumour necrosis factor-alpha in plaque psoriasis were deficient., Conclusions: Differential expression and regulatory functioning for inflammatory cytokine production by Foxp3+ Tregs may imply a different immunopathogenesis for plaque and guttate psoriasis.

Objectives: Psoriasis is common in childhood. The aim of this study was to present the clinical and epidemiological profile of childhood psoriasis in China., Methods: A total of 277 childhood psoriasis patients younger than 16 years old were enrolled. Statistical analysis and heritability were performed using EPI INFO 6.0, spss 10.0 and Falconer's method., Results: The median age was 11 years. The male : female ratio was 1:1.13. The median age of onset was 10 years. Of the patients, 48.7% had previous episodes of psoriasis. Of the 277 children with psoriasis, 68.6% had plaque-type psoriasis, 28.9% had guttate psoriasis, 1.1% presented pustular forms of psoriasis and 1.4% had erythroderma. The extensor surface of the extremities was the most frequently affected site in our patients, followed by the appearance of lesions on the scalp. A positive family history of psoriasis was found in 34.3% patients. The prevalence of psoriasis in first- and second-degree relatives was 7.0% and 1.0%, respectively. The heritability of psoriasis in first- and second-degree relatives was 72.67% and 55.18%, respectively., Conclusion: Our epidemiologic studies offer the information about Han Chinese distribution, which provide clues to describe psoriasis in children.

Background Although elevated serum IgE levels have been reported in psoriasis, the role of IgE in psoriasis still needs to be clarified. Objectives To analyse serum total IgE levels in addition to the presence and distribution of IgE and Fcε RI in psoriatic lesions, and to investigate alteration of IgE and Fcε RI after successful systemic treatment. Methods Total serum IgE levels were determined using enzyme-linked immunosorbent assay. The expression and localization of IgE and Fcε RI was investigated using immunohistochemistry and double immunofluorescence. Results Elevated total serum IgE levels were found in 39% of patients with psoriasis. The levels of total serum IgE were significantly higher in male patients compared with female patients. Furthermore, total serum IgE levels decreased after successful systemic treatment. A positive correlation between IgE+ and Fcε RI+ cells and a significant increase of these cells was found in psoriatic lesions when compared with normal skin. Interestingly, IgE+ and Fcε RI+ cells decreased significantly after successful therapy with ustekinumab. IgE and Fcε RI were coexpressed on mast cells, epidermal Langerhans cells, dermal dendritic cells, macrophages and a small number of neutrophils. Conclusions IgE might participate in the development of psoriasis by activating Fcε RI-bearing cells. [ABSTRACT FROM AUTHOR]

Background Psoriasis is a chronic, relapsing, inflammatory skin disease, in which regulatory T cells (Tregs) play an important role. Recently, human Treg ectoenzymes ( CD39/ CD73) have been reported to mediate the suppressive activity of Tregs. Aim To investigate the proportions of CD39/ CD73 expressing Foxp3+ regulatory T cells in different types of psoriatic lesions. Methods Immunohistochemical staining was used to analyse expression of Foxp3, CD39 and CD73 in biopsy tissue from healthy controls and from patients with different types of psoriasis. Results In normal control biopsies, CD39+ cells were scattered throughout the epidermis and dermis, while CD73+ cells were localized predominantly in the dermis. The proportion of cells that were both CD39+ and Foxp3+ was significantly lower in pustular psoriasis ( PP) and erythrodermic psoriasis ( EP) than in psoriasis vulgaris ( PV) (25.0 ± 2.6%, 26.5 ± 2.0% and 45.1 ± 3.5%, respectively; P < 0.001). Likewise, CD73+Foxp3+ cells were lower in PP and EP than in PV (6.2 ± 1.9%, 11.6 ± 2.8% and 17.7 ± 2.3% respectively, P < 0.001). There were no significant differences in the population size of double-staining cells in EP compared with PP. Conclusion The relative reduced expressions of CD39 and CD73 within Foxp3+ Tregs may imply a different immunopathogenesis for different psoriatic lesions. [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a common skin disease that affects about 2% to 3% of people. The cause is unknown and believed to involve the genes and immune system, and the treatments we use now can control psoriasis but do not cure it. This study, from China, aimed to find out the effect and mechanism (way of working) of a drug called methotrexate on cells called regulatory T cells, which have the power to fight back and calm down the skin, as well as its relationship with the pathway of a chemical in the body called adenosine, which is a target in psoriasis therapy. Regulatory T cells (and effector T cells, which can trigger psoriasis) were isolated from the blood of healthy people and patients with psoriasis. Various laboratory tests were used to examine the effect of methotrexate on the adenosine pathway. The authors found that psoriasis patients have regulatory T cells with decreased function, meaning they do not work so well, and reduced CD73 level, which was the starting section of adenosine pathway. Furthermore, methotrexate could restore the immunosuppressive function of regulatory T cells by affecting part of the adenosine pathway, including increasing CD73 expression and regulating its related signal pathway. In conclusion, the study deepens doctors' and patients' understanding of methotrexate in the treatment of psoriasis, and contributes to our understanding of psoriasis. Linked Article: Yan et al. Br J Dermatol 2018; 179:896–905 [ABSTRACT FROM AUTHOR]