Long Non-Coding RNA Promotes CCL5 Secretion and Cell Migration of Monocyte-Derived Dendritic Cells via PI3K/AKT/mTOR Pathway in Systemic Lupus Erythematosus.

Purpose: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that seriously endangers human health. Long non-coding RNAs (lncRNAs) have been found to exhibit strong regulatory functions in cell physiology and maturation of dendritic cells (DCs). Hence, this study tried to reveal the underlying roles of one lncRNA, , in modulating DC functions and its involvement with CCL5 secretion in SLE pathogenesis.

Methods: The expression levels of were measured using qPCR in cultivated monocyte-derived dendritic cells (moDCs). Flow cytometry, ELISA, and Transwell chamber experiments were performed to assess various biological functions of moDCs. RNA-seq analysis was conducted to investigate transcriptional alterations in cells overexpressing and negative control cells. Gene Set Enrichment Analysis (GSEA) was utilized to predict potentially involved signaling pathways, which were subsequently confirmed by Western Blotting. Rescue experiments were carried out where the expression of and PI3K/AKT/mTOR pathway were altered simultaneously.

Results: was significantly upregulated in moDCs from SLE patients, and it exhibited a positive correlation with SLE Disease Activity Index (SLEDAI) scores. Additionally, elevated levels of CCL5 were detected in both plasma and moDC supernatants of SLE patients. Overexpression of stimulated moDCs to secrete higher levels of CCL5, and it enhanced the migration ability of moDCs as well as their capacity to attract CD4+ naïve T cells. GSEA analysis of RNA profiles indicated the potential involvement of the PI3K/AKT/mTOR pathway in regulation, which was further validated by Western Blotting. The rescue experiments demonstrated that the effects of on multiple functions of moDCs were attenuated when the PI3K/AKT/mTOR pathway was disrupted.

Conclusion: This study elucidated the role of in orchestrating DC migration and the recruitment of CD4+ T cells by enhancing CCL5 secretion through activating PI3K/AKT/mTOR pathway, which provides insights into potential molecular targets for SLE diagnosis and treatment.