Search

There have been reports of association between psoriasis and psychological illnesses. Nevertheless, it is not easy to draw conclusions with high quality causality from conventional observational studies. The objective of this study was to evaluate the causality of psoriasis and psychological illnesses. All summary-level data from genome-wide association studies for psoriasis and psychological illnesses were collected from Neale Lab and MRC Integrative Epidemiology Unit. Bidirectional Mendelian randomization analysis was performed to determine the random orientation with an independent genetic variation. The main estimated effects are derived using Inverse-Variance Weighted, weighted median, and MR Egger methods. Multiple data sets were validated against each other, and a series of sensitivity studies were conducted to ensure the reliability of the results. Mendelian randomization analysis revealed a causal effect of psoriasis [odds ratio (OR) 1·34, 95% confidence interval (CI) 1·21–1·46, P < 0.001; and OR 1.28, CI 1.17–1.39, P < 0.001] on psychological illnesses, and vice versa (OR 1.23, CI 1.14–1.31, P < 0.001; and OR 1.21, CI 1.11–1.31, P < 0.001). The results were supported by a series of sensitivity analyses. The findings of this Mendelian randomization study support a causal effect between psoriasis and psychological illnesses, and vice versa. [ABSTRACT FROM AUTHOR]

• Phenotype of Tph17 cells is activated and proliferative in psoriasis vulgaris. • Tph17 cells and plasma CXCL13 could be biomarkers for evaluating the severity of psoriasis vulgaris. • Tph17 cells and the CXCL13/CXCR5 axis might represent new immunotherapeutic targets for psoriasis vulgaris. Recently, a new subgroup of T cells, named peripheral helper T (Tph) cells, has been implicated in autoimmune pathogenesis. An imbalance of Tph cell subsets influences the severity of immune-related diseases. However, the characteristics and roles of Tph cell subsets in psoriasis remain unknown. Programmed cell death 1-positive, chemokine C-X-C receptor (CXCR) 5-negative Tph cells can be divided into 3 subgroups based on differential expression of chemokine CXCR3 and chemokine C-C receptor (CCR) 6. CXCR3+CCR6− Tph cells are classified as Tph1, CXCR3−CCR6− Tph cells are classified as Tph2, and CXCR3−CCR6+ Tph cells are classified as Tph17. In this study, conditions of circulating Tph cell subsets and CD4+CXCR5+ follicular helper T (Tfh) cells in 27 patients with psoriasis and 13 healthy individuals were detected by flow cytometry. The level of plasma chemokine C-X-C ligand (CXCL) 13 was measured by enzyme-linked immunosorbent assay. The correlations between the above indexes and disease severity were explored. In the peripheral blood of patients with psoriasis, Tph17 cells had an activated, proliferative phenotype; the quantity of the cells correlated with disease severity. Plasma CXCL13 levels were elevated in psoriasis and associated with disease severity and the frequency of Tph17 cells. CD4+CXCR5+ Tfh cells were increased in patients and positively correlated with disease severity, the frequency of Tph17 cells, and plasma CXCL13 levels. Our results suggest that Tph17 cells and the CXCL13/CXCR5 axis may be involved in the pathogenesis of psoriasis and represent new immunotherapeutic targets for treating psoriasis. [ABSTRACT FROM AUTHOR]

Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism. In total, 120 and 212 DEGs were identified in PS and RA, respectively, and 31 shared DEGs were identified. Bioinformatics analysis indicated that the cytokine imbalance relevant to key molecules (such as extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), colony-stimulating factor 3 (CSF3), interleukin- (IL-) 6, and interferon gene (IFNG)) and canonical signaling pathways (such as the complement system, antigen presentation, macropinocytosis signaling, nuclear factor-kappa B (NF-κB) signaling, and IL-17 signaling) was responsible for the common comprehensive mechanism of PS and RA. Our findings provide a better understanding of the pathogenesis of PS and RA, suggesting potential strategies for treating and preventing both diseases. This study may also provide a new paradigm for illuminating the common pathogenesis of different diseases. [ABSTRACT FROM AUTHOR]

Circulating T follicular helper (Tfh) cells in the blood are counterparts to conventional Tfh cells in germinal centres. Similarly to conventional Tfh cells, circulating Tfh cells provide helpful signals for B cells. Circulating Tfh cells can be divided into three subpopulations, including Tfh17 (CXCR3-CCR6+), Tfh1 (CXCR3 + CCR6-), and Tfh2 (CXCR3-CCR6-) cells, based on differences in CXCR3 and CCR6 expression. Recent studies have demonstrated that alterations in circulating Tfh cell subsets have significant effects on the progression of numerous autoimmune diseases. To address the role of circulating Tfh cells in psoriasis, we used flow cytometry to analyse frequencies of circulating Tfh cell subsets and levels of IL-21 receptor (IL-21R) expression on B cells in 32 patients with psoriasis vulgaris and 13 sex- and age-matched healthy controls. We observed dynamic changes in Tfh17 cell frequency and disease severity in 10 psoriasis patients during a 6-month treatment. Our results demonstrate that the frequency of Tfh17 cells was significantly increased in psoriasis patients and was positively correlated with psoriasis area and severity index (PASI) score, a marker of disease severity ( P < 0.05). During the follow-up period, the frequencies of Tfh17 cells decreased, and reductions in PASI scores were observed. Moreover, IL-21R expression on B cells was significantly increased in patients with psoriasis vulgaris ( P < 0.05). Interestingly, IL-21R levels on B cells were correlated with both PASI score and the frequency of Tfh17 cells ( P < 0.05). In conclusion, this study is the first investigation of the distribution of circulating Tfh subsets in psoriasis. These results deepen our understanding of the immune state of psoriasis patients. Our data also indicate that Tfh17 cells may not be good biomarkers for diagnosing psoriasis but may be potential biomarkers of disease severity in psoriasis. [ABSTRACT FROM AUTHOR]