Wang-Dong Xu

Role of the TWEAK/Fn14 pathway in autoimmune diseases.

TNF-like weak inducer of apoptosis (TWEAK) is a member of the TNFSF ligands, initially synthesized as a type II transmembrane protein. TWEAK signaling occurs via binding to Fn14, a type I transmembrane receptor belonging to the TNF receptor superfamily. TWEAK/Fn14 activation controls several cellular responses, including proliferation, angiogenesis, induction of inflammatory cytokines. Studies have indicated that expression of TWEAK/Fn14 was dysregulated in autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease. Functional analysis suggested that TWEAK/Fn14 may play an important role in the development of these diseases. In this review, we discuss the TWEAK/Fn14 pathway and its significant role in autoimmune disorders. The information obtained may lead to a better understanding of the insights into TWEAK/Fn14 in these autoimmune diseases.

Association of Interleukin-23 receptor gene polymorphisms with susceptibility to Crohn's disease: A meta-analysis.

Studies investigating the association between Interleukin-23 receptor (IL-23R) gene polymorphisms and Crohn’s disease (CD) report conflicting results. Thus, a meta-analysis was carried out to assess the association between the IL-23R polymorphisms and CD. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CIs) was used to estimate the strength of association. Finally, a total of 60 case-control studies in 56 articles, involving 22,820 CD patients and 27,401 healthy controls, were included in the meta-analysis. Overall, a significant association was found between all CD and the rs7517847 polymorphism (OR = 0.699, 95% CI = 0.659 ~ 0.741, P < 0.001). Meta-analysis of the rs11209026, rs1343151, rs10489629 and rs11465804 polymorphisms indicated the same pattern as for rs7517847. Meta-analysis showed an association between the rs10889677A allele and CD (OR = 1.393, 95% CI = 1.328 ~ 1.461, P < 0.001). Similarly, meta-analysis of the rs2201840, rs1004819, rs1495965 and rs11209032 polymorphisms revealed the same pattern as that shown by meta-analysis of rs10889677. Stratification by ethnicity revealed that IL-23R gene polymorphisms were associated with CD in the Caucasian group, but not in Asians. In summary, the meta-analysis suggests a significant association between IL-23R polymorphisms and CD, especially in Caucasians.

Cervical spine involvement risk factors in rheumatoid arthritis: a meta-analysis

This study aims to discuss risk factors associated with cervical spine involvement (CSI) in patients with rheumatoid arthritis (RA).

Emerging role of IL-35 in inflammatory autoimmune diseases

Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis. In addition, functional analysis suggested that IL-35 is critical in the onset and development of these diseases. Therefore, the present study will systematically review what had been occurred regarding IL-35 in inflammatory autoimmune disease. The information collected will help to understand the biologic role of IL-35 in immune cells, and give information about the therapeutic potential of IL-35 in these diseases.

Role of microRNA-155 in rheumatoid arthritis

MicroRNAs (miRNAs) are a recently discovered class of post‐transcriptional regulators that induce target messenger RNA degradation or translation inhibition. miRNA‐155 (miR‐155) is an important regulator of immune cells both in humans and mice, by which these cells play critical roles in the pathogenesis of rheumatoid arthritis (RA). Recent findings showed that expression of miR‐155 was elevated in RA patients and arthritis models. Moreover, miR‐155 overexpression or knockdown performed significantly in the development of arthritis. This review summarizes the recent findings with respect to miR‐155 in immune responses and the underlying mechanisms responsible for miR‐155‐related autoimmune arthritis. Hopefully the information obtained will benefit the development of novel therapeutic strategies.

Interleukin-2-inducible T-cell kinase expression and relation to disease severity in systemic lupus erythematosus.

BACKGROUND Interleukin-2 inducible T-cell kinase (ITK) is expressed in T cells, and plays an important role in autoimmune inflammatory diseases through regulating the balance of Th17/Treg. However, its role in human systemic lupus erythematosus (SLE) remains unclear. The present study aims to measure the activation status of ITK in T cells from SLE patients and healthy controls, and identify its possible correlation to disease severity. We also discuss the serum levels of Th17, Treg related cytokines including IL-17, IL-21, IL-22, IL-10, analyzing correlation between ITK and Th17/Treg related cytokines. METHODS Peripheral blood samples were drawn from 42 patients with SLE and 43 healthy blood donors, and the phosphorylation of ITK protein was studied in T cells using flow cytometry. In addition, serum levels of Th17/Treg related cytokines were studied with enzyme-linked immunosorbent assay (ELISA). RESULTS Percentages of CD4+pITK+ T cells, CD8+pITK+ T cells were higher in SLE patients compared with controls, and were positively related to disease activity, some clinical and laboratory parameters. Percentages of CD4+pITK+ T cells, CD8+pITK+ T cells were more prominent in active SLE patients compared with less active patients. Serum levels of Th17 and Treg related cytokines were higher in patients compared with controls. CD4+pITK+ T cells were related to levels of IL-17, IL-21. CONCLUSION These data indicate that increased ITK expression could act as a disease activity marker and as a risk factor for involvement in SLE, but it still needs further study to confirm.

Interactions between canonical Wnt signaling pathway and MAPK pathway regulate differentiation, maturation and function of dendritic cells

Antigen-presenting dendritic cells interpret environmental signals to orchestrate local and systemic immune responses. In this study, the roles of Wnt proteins and their signaling pathway members in the maturation and function of monocyte-derived DCs were investigated. The present study showed higher expression of β-catenin, as well as pGSK-3β in DCs than those in monocytes. Wnt3a, Wnt5a and inhibition of GSK-3β promoted differentiation of DCs, but inhibited maturation of DCs. GSK-3β induced DCs maturation with unconventional phenotypes. Together with β-catenin silence, these treatment lead to reduced secretion of cytokines and chemokines except for IL-10 in comparison with LPS treatment, and significantly promoted proliferation of T cells. Wnt3a and inhibition of GSK-3β increased expression of MAPK signalings (p-ERK, p-p38, p-JNK). However, inhibition of MAPK signalings in turn differently regulated Wnt signaling proteins expression. These data suggest that Wnt pathway regulates DCs differentiation, maturation and function with interaction of MAPK signaling pathways.

Plasma interleukin-38 in patients with rheumatoid arthritis

&NA; Previous studies have indicated that interleukin‐38 (IL‐38) is involved in rheumatoid arthritis (RA). The present study aims to assess plasma levels of IL‐38 in RA and discuss the potential of IL‐38 as a biomarker for RA. Protein concentrations of IL‐38 were examined by enzyme‐linked immunosorbent assay, and the mRNA level of IL‐38 was tested by quantitative real‐time polymerase chain reaction. Plasma IL‐38 was first compared in a training cohort, including 130 RA patients and 53 healthy controls, given the optimal cutoff. Then, we validated the levels of IL‐38 in a further cohort of 519 patients, including 250 with RA, 63 systemic lupus erythematosus, 62 primary Sjogrens syndrome, 51 gout, 63 osteoarthritis, and 30 psoriatic arthritis, as well as 60 healthy controls. To further discuss the changes in IL‐38 after treatment and the relationship with disease activity, we tested IL‐38 expression in RA patients from the training cohort under follow‐up. In the training cohort, plasma levels of IL‐38 were higher in RA patients compared with healthy controls (681.00 [234.45–826.47] versus 152.04 [70.06–246.80] pg/mL, P < 0.001). The IL‐38 mRNA level was elevated in RA patients as compared with healthy controls (P < 0.001). Expression of IL‐38 was significantly higher in RA patients compared with that in non‐RA patients in the validation cohort (all P < 0.001). Treatment significantly reduced IL‐38 expression. IL‐38 expression was related to parameters of inflammation both at baseline and in the follow‐up studies. The area under the curve (AUC) of the receiver‐operating characteristic curve showed that IL‐38 may be a potential biomarker for RA. At the optimal cutoff value of 341.90 pg/mL, the sensitivity, specificity, and AUC were 72.30%, 90.60%, and 0.840, respectively, in the training cohort. Similar results were noted in the validation cohort. In conclusion, IL‐38 expression correlated with RA disease activity, and plasma IL‐38 might be a promising diagnostic biomarker for RA.

Analysis of blood glucose distribution characteristics in a health examination population in Chengdu (2007–2015)

Abstract With socioeconomic growth and cultural changes in China, the level of blood glucose may have changed in recent years. This study aims to detect the blood glucose distribution characteristics with a large size of health examination population. A total of 641,311 cases (360,259 males and 281,052 females) more than 18 years old during 2007 to 2015 were recruited from the Health Examination Center at West China hospital, Sichuan University. The percentage of cases with abnormal glucose level and the mean level of glucose were significantly increased since 2007 to 2015 overall. The percentage of cases with abnormal glucose level in males was significantly higher than that in females every year, and the percentage of cases with abnormal glucose level in aged population was higher than the young population. In addition, the mean level of glucose was higher in aged population with normal level of glucose than the young population with normal level of glucose, and the mean level of glucose was higher in males with normal level of glucose than the females with normal level of glucose. The population showed an increased level of blood glucose. Some preventive action may be adopted early and more attention can be paid to them.

Fli-1, a Functional Factor Performed in Autoimmune Lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease. The friend leukemia insertion site 1 (Fli-1) belongs to the Ets family of transcription factors. Recent findings suggested that expression of Fli-1 was abnormal in SLE patients and lupus mice. In addition, functional analysis indicated that Fli-1 plays a key role in the development of this complex autoimmune disorder. Here, we review the updated evidence indicating the roles of Fli-1 in autoimmune lupus. Hopefully, the information obtained may result in a better understanding of the pathogenesis of the systemic autoimmune disease.