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.

Extracellular Vesicles (EVs) are small vesicles that can be actively secreted by most cell types into the extracellular environment. Evidence indicates that EVs can carry microRNAs (miRNAs), long non-coding RNAs (lncRNAs), tRNA-derived small RNAs (tsRNAs), proteins, and lipids to target cells or tissue organizations. Latest studies show that EVs play a vital role in the immune modulation and may contribute to the pathogenesis of autoimmune diseases. Systemic lupus erythematosus (SLE) is a common autoimmune disease characterized by abnormal T cell activation and sustained production of autoantibodies against self-antigens, resulting in inflammation and damage to multiple systems. Pathogenic mechanisms of SLE, however, are still not well understood. In this review, we summarize the latest research advances on the functions and mechanisms of EVs, and its role in the pathogenesis, diagnosis, and treatment of SLE.

Objective:The mechanism of CD4⁺T-cell dysfunction in systemic lupus erythematosus (SLE) has not been fully understood. Increasing evidence show that long noncoding RNAs (lncRNAs) can regulate immune responses and take part in some autoimmune diseases, while little is known about the lncRNA expression and function in CD4⁺T of SLE. Here, we aimed to detect the expression profile of lncRNAs in lupus CD4⁺T cells and explore the mechanism that how lincRNA00892 in CD4⁺T cells is involved in the pathogenesis of SLE.Methods:The expression profiles of lncRNAs and mRNAs in CD4⁺T cells from SLE patients and healthy controls were detected by microarray. LincRNA00892 and CD40L were chosen for validation by quantitative real-time PCR (qRT-PCR). Coexpression network was conducted to predict the potential target genes of lincRNA00892. Then lincRNA00892 was overexpressed in normal CD4⁺T cells via lentivirus transfection. The expression of lincRNA00892 was detected by qRT-PCR. The expression of CD40L was detected by qRT-PCR, western blotting, and flow cytometry, respectively. The expression of CD69 and CD23 was measured by flow cytometry. The secretion of IgG was determined by enzyme-linked immunosorbent assay (ELISA). The proteins targeted by lincRNA00892 were measured by RNA pulldown and subsequent mass spectrometry (MS). The interaction between heterogeneous nuclear ribonucleoprotein K (hnRNP K) and lincRNA00892 or CD40L was detected by RNA immunoprecipitation (RIP) assay.Results:A total of 1887 lncRNAs and 3375 mRNAs were found to be aberrantly expressed in CD4⁺T cells of SLE patients compared to healthy controls. LincRNA00892 and CD40L were confirmed to be upregulated in CD4⁺T cells of SLE patients by qRT-PCR. The lncRNA–mRNA coexpression network analysis indicated that CD40L was a potential target of lincRNA00892. Overexpression of lincRNA00892 enhanced CD40L protein levels while exerting little influence on CD40L mRNA levels in CD4⁺T cells. In addition, lincRNA00892 could induce the activation of CD4⁺T cells. Furthermore, lincRNA00892 led to the activation of B cells and subsequent secretion of IgG in a CD4⁺T-cell–dependent manner. Finally, hnRNP K was found to be among the proteins pulled down by lincRNA00892, and hnRNP K could bind to lincRNA00892 or CD40L directly.Conclusion:Our results showed that the lncRNA expression profile was altered in CD4⁺T cells of SLE. LincRNA00892 possibly contributed to the pathogenesis of SLE by targeting hnRNP K and subsequently upregulating CD40L expression to activate CD4⁺T and B cells. These provided us a potential target for further mechanistic studies of SLE pathogenesis.

Introduction: Systemic lupus erythematosus is a heterogeneous autoimmune disease. A burst of autoimmune reactions in various systems can lead to severe clinical conditions closely associated with mortality. T cells serve as mediators that drive the occurrence and maintenance of inflammatory processes. Methods: In this work, we employed single-cell transcriptome sequencing (scRNA-seq) involving 27704 cells from the brain and spleen tissues of MRL/lpr mice and 25355 healthy controls from BALB/c mice to explore the heterogeneity of T cells and their migration from the spleen to the brain. Results: We identified a distinct group of double-negative T cells in systemic lupus erythematosus (SLE) mice that significantly expressed Eomes and other specific markers. We used the analysis of pseudotime trajectory and enrichment to show that double-negative T cells in SLE mice are strongly associated with cellular senescence and exhaustion. Additionally, we focused on the interactions among DNT, astrocytes, and microglia in the mice brain. We observed greater expression of MDK-related ligand‒receptor pairs between astrocytes and double-negative T cells, indicating that MDK may be a therapeutic target for treating neuroinflammation in SLE. Discussion: This research sheds light on the intricate dynamics of immune responses in mice with SLE, specifically highlighting the role of double-negative T cells and their connection to cellular senescence. The exploration of interactions between T cells, astrocytes, and microglia in the mice brain unveils potential avenues for therapeutic intervention, particularly in addressing neuronal inflammation in SLE.