Recent studies have shown that alterations in the function of dendritic cells (DCs) are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanism of the alteration remains unclear. We cultured monocyte-derived DCs (moDCs) in vitro and examined the cytokines and chemokines in the supernatants of moDCs in negative controls (NC) and SLE patients in active phase. We then profiled microRNAs (miRNAs) of LPS-stimulated moDCs in SLE patients and used real-time PCR to verify the differentially expressed miRNAs. A lentiviral construct was used to overexpress the level of miR-142-3p in moDCs of NC. We examined the cytokines and chemokines in the supernatants of moDCs overexpressing miR-142-3p and used Transwell test, flow cytometric analysis and cell proliferation to observe the impact on CD4+ T cells in moDC-CD4+T cell co-culture. moDCs in patients with SLE secreted increased level of IL-6, CCL2 and CCL5, with attraction of more CD4+ T cells compared with NC. We found 18 differentially expressed microRNAs in moDCs of SLE patients by microarray, and target gene prediction showed some target genes of differentially expressed miRNAs were involved in cytokine regulation. miR-142-3p was verified among the highly expressed miRNAs in the SLE group and overexpressing miR-142-3p in moDCs of the NC group caused an increase of SLE-related cytokines, such as CCL2, CCL5, CXCL8, IL-6 and TNF-α. Moreover, moDCs overexpressed with miR-142-3p resulted in attraction of an increased number of CD4+ T cells and in suppression of the proportion of Tregs in DC-CD4+T cell co-culture whereas the proliferation of CD4+T cells was not altered. The results demonstrated a role for miR-142-3p in regulating the pro-inflammatory function of moDCs in the pathogenesis of SLE. These findings suggested that miR-142-3p could serve as a novel therapeutic target for the treatment of SLE.

Monocyte-derived dendritic cells (moDCs) play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Aberrant expression of long noncoding RNAs (lncRNAs) could affect the function of moDCs. The aim of this study was to explore the lncRNA expression profile in moDCs of SLE patients to provide new insights into SLE. LncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in moDCs of SLE patients compared with normal controls. Bioinformatics analysis was also performed. Quantitative polymerase chain reaction (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship between these aberrantly expressed lncRNAs and SLE disease activity index (SLEDAI) scores. According to the gene expression profiles, 163 lncRNAs were differentially expressed between SLE and normal controls, including 118 that were upregulated and 45 that were downregulated. A total of 137 mRNAs were differentially expressed in moDCs of patients with SLE, including 83 that were upregulated and 54 that were downregulated. Furthermore, qPCR data showed that lncRNA ENST00000604411.1 (18.23-fold, P < 0.001) and ENST00000501122.2 (1.96-fold, P < 0.001) were upregulated and the other two lncRNAs, lnc-HSFY2–3:3 (0.42-fold, P < 0.001) and lnc-SERPINB9–1:2 (0.50-fold, P = 0.040), were downregulated in moDCs of SLE patients. The expression levels of ENST00000604411.1 (r = 0.593, P = 0.020) and ENST00000501122.2 (r = 0.539, P = 0.038) were positively correlated with the SLEDAI score, respectively. The results indicate that the abnormal expression of lncRNAs in moDCs may be involved in the pathological processes of SLE. The expression level of ENST00000604411.1 and ENST00000501122.2 may have potential value for the assessment of disease activity in SLE.

Background: Psoriasis is a chronic inflammatory dermatosis. The hyperproliferation and hyperkeratosis of keratinocytes is a key step in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) and mRNAs regulate gene expression in various biological process, including the function of keratinocytes. This research investigated the expression profile of lncRNAs and mRNAs in keratinocytes of patients with psoriasis vulgaris. Methods: The expression of lncRNAs and mRNAs in keratinocytes from patients with psoriasis vulgaris and healthy patients was examined and compared using microarrays. Quantitative polymerase chain reaction (qPCR) and bioinformatic analysis was also performed. DAVID and KEGG were used to analyze the gene function. The competing endogenous RNA (ceRNA) network was also constructed. Results: A total of 48 lncRNAs and 17 mRNAs were differentially expressed in keratinocytes of psoriasis vulgaris. Quantitative PCR data showed that the expression of lnc-AGXT2L1-2:2 (P=0.009) and NR_027032 (P=0.033) was up-regulated in psoriasis vulgaris. The lncRNA-miRNA-mRNA interaction network was established. The mRNA showing the most connections with the lncRNAs and miRNAs was CEP104. The miRNA showing the most connections with the lncRNAs and mRNAs was miR-484. The lncRNA showing the most connections with miRNAs and mRNAs was ENST00000494887. Conclusions: The identification of the differentially expressed lncRNAs and mRNAs in psoriasis vulgaris provides significant insights into the pathogenesis of the disease.

Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577, p = 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124, p = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664, p = 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics.

Erythroderma psoriasis (EP) is a rare and severe form of psoriasis, which is a chronic inflammatory skin disease that usually occurs simultaneously with cardiovascular disease (CVD). Metabolic syndrome (MetS) is a significant precursor of CVD. This study was to investigate the association between EP and MetS in the Chinese population. We conducted a retrospective study on 86 consecutive patients with EP and 100 healthy controls from Huashan Hospital between 2013 and 2018. Demographic, biochemical parameters for MetS, and other relevant data including the severity of EP, family history of EP, age of onset, and treatment history involved in those individuals were recorded. The prevalence of MetS in erythrodermic psoriatic patients was 88.37%, which was significantly higher than that of controls (P &lt; 0.0001). Erythrodermic psoriatic patients also had a higher prevalence of MetS components, including abdominal obesity, dyslipidemia and hypertension, whereas hyperglycemia was similar. Adjusted for confounding factors, MetS, abdominal obesity, hypertension, smoking and alcohol use were positive independent predictors of EP (odds ratio > 1, P < 0.05). The area under the receiver operating characteristic curve calculated from determined risk factors for predicting the EP’s incidence was 0.934 (95% CI 0.902-0.966). There was no correlation between the severity of EP and the prevalence of MetS. Compared with patients with mild EP, patients with moderate-to-severe EP had higher body mass index, waist circumstance and blood pressure (P < 0.05). We concluded that the prevalence of MetS and its components was higher in patients with EP. MetS an independent predictor of EP, which can favor CVD and should be encouraged to correct these cardiovascular risk factors aggressively for managing EP.