Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with significant therapeutic challenges. Recent studies suggest that dihydroartemisinin (DHA), a traditional Chinese medicine known for its anti-malarial properties, may be beneficial for SLE treatment, although its precise mechanism remains unclear. This study aimed to investigate the effects of DHA on the cellular composition and molecular events of splenic T cells and B cells in MRL/lpr mice, a widely used SLE model. Methods: T cells and B cells isolated from the spleens of three DHA-treated mice and three control mice underwent single-cell RNA sequencing (scRNA-seq) using the 10× Genomics Chromium system. Comprehensive analyses included cell clustering, signaling pathway enrichment, pseudotime trajectory analysis, and cellular communication assessment using unbiased computational methods. Results: DHA treatment significantly reduced kidney inflammation and altered the proportions of splenic T cells and B cells, particularly decreasing plasma cells. Molecular profiling of effector CD4+ T cells showed a significant reduction in several inflammation-related signaling pathways in DHA-treated mice. Cellular communication analysis indicated altered interactions between effector CD4+ T cells and B cells in MRL/lpr mice after DHA treatment. Conclusions: Our findings reveal changes in cellular composition and signaling pathways in splenic T cells and B cells of MRL/lpr mice following DHA treatment. DHA may inhibit B-cell differentiation into plasma cells by modulating effector CD4+ T cells, potentially through the regulation of HIF1α and ligand–receptor interactions, enhancing our understanding of DHA’s mechanisms in SLE treatment.

Objective: This study aimed to evaluate the expression status of miR-132-3p in CD4⁺ T cells in patients with systemic lupus erythematosus (SLE) and explore its potential role in SLE development. Methods: The study included 60 patients with SLE and 30 healthy controls. miR-132-3p expression in CD4⁺ T cells was detected by real-time quantitative reverse transcription polymerase chain. Bioinformatics analyses were employed to predict target genes and explore the potential role of miR-132-3p. The associations between miR-132-3p levels and SLE Disease Activity Index (SLEDAI) score, as well as laboratory characteristics, were analyzed. Results: miR-132-3p levels in CD4⁺ T cells were significantly higher in patients with SLE compared with healthy controls. Bioinformatics analysis identified FOXO1 as a potential target gene of miR-132-3p, with a particular emphasis on the FOXO signaling pathway. miR-132-3p up-regulation in CD4⁺ T cells was associated with high SLEDAI score, high anti-double-stranded DNA levels, low C3 and C4 levels, positive anti-ribosomal P, and high 24-hour urinary protein levels in patients with SLE. Conclusions: miR-132-3p may contribute to CD4⁺ T cell dysregulation during SLE by targeting FOXO1 and could potentially be used to assess disease severity.

Lupus erythematosus (LE) comprises various autoimmune inflammatory diseases, with significant overlap between cutaneous LE (CLE) and systemic LE (SLE). A key feature of both CLE and SLE is UV photosensitivity, particularly in UV-exposure-related skin inflammation. Despite this, reliable and objective UVB photosensitivity indicators closely correlating with LE activity have yet to be identified, and the underlying cellular and molecular mechanisms linking UVB sensitivity with LE onset and progression remain unclear. We discovered that ultraviolet B minimal erythema dose (UVB-MED), a quantitative photosensitivity measure, is a significant and independent risk factor for SLE activity, demonstrating a negative correlation with SLEDAI (r = -0.58, P < 0.0001). Comprehensive transcriptomic analyses of large-scale CLE and SLE samples revealed more pronounced and extensive UVB-response gene dysregulation in skin tissues compared to blood. Additionally, 14 lupus activity-correlated, UVB-response genes (UVBACGs) were identified, including eight interferon-stimulated genes (IRF7, ISG20, ISG15, IFI44, IFITM1, MX1, LY6E, OASL) and others (JUN, PTTG1, HLA-F, CAV1, HOPX, RPL3), with dysregulation evident in both skin and blood cells, particularly immunocytes. Conventional LE therapies were found to be associated with these genes and may potentially regulate them, thereby contributing to therapeutic effects. These findings highlight the role of UVB in triggering autoimmune inflammation in the skin, which may subsequently spread to systemic inflammation via immune cells and factors. UVBACGs play a critical role in this process and may serve as targets for precise LE therapies, providing insight into the link between UVB photosensitivity and LE progression.