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Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease recognized by elevated activity of autoimmune cells, loss of tolerance, and decreased regulatory T cells producing inhibitory cytokines. Despite many efforts, the definitive treatment for lupus has not been fully understood. Curcumin (CUR) and berberine (BBR) have significant immunomodulatory roles and anti-inflammatory properties that have been demonstrated in various studies. This study aimed to investigate the anti-inflammatory properties of CUR and BBR on human monocyte-derived dendritic cells (DCs) with an special focus on the maturation and activation of DCs., Methods: Human monocytes were isolated from the heparinized blood of SLE patients and healthy individuals, which were then exposed to cytokines (IL-4 and GM-CSF) for five days to produce immature DCs. Then, the obtained DCs were characterized by FITC-uptake assay and then cultured in the presence of CUR, BBR, or lipopolysaccharide (LPS) for 48 h. Finally, the maturation of DCs was analyzed by the level of maturation using flow cytometry or real-time PCR methods., Results: The results showed promising anti-inflammatory effects of CUR and BBR in comparison with LPS, supported by a significant reduction of not only co-stimulatory and antigen-presenting factors such as CD80, CD86, CD83, CD1a, CD14, and HLA-DR but also inflammatory cytokines such as IL-12., Conclusion: CUR and BBR could arrest DC maturation and develop a tolerogenic DC phenotype that subsequently promoted the expression of inhibitory cytokines and reduced the secretion of proinflammatory markers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)