Alternatively activated dendritic cells derived from systemic lupus erythematosus patients have tolerogenic phenotype and function

- Vitamin D3 and dexamethasone can generate tolerogenic dendritic cells from lupus monocytes.
- These alternatively activated dendritic cells induce IL-10 producing Treg from naïve T cells.
- They attenuate pro-inflammatory profile with suppressed proliferation of memory T cells.

Tolerogenic dendritic cells (DCs) are potential cell-based therapy in autoimmune diseases. In this study, we generated alternatively activated DCs (aaDCs) by treating monocyte-derived DCs from patients with systemic lupus erythematosus (SLE) and healthy subjects with combination of 1,25 dihydroxyvitamin D(3) (vitD3) and dexamethasone followed by lipopolysaccharide-induced maturation. Lupus aaDCs were found to acquire semi-mature phenotype that remained maturation-resistant to immunostimulants. They produced low level of IL-12 but high level of IL-10. They had attenuated allostimulatory effects on T cell activation and proliferation comparable to normal aaDCs and demonstrated differential immunomodulatory effects on naïve and memory T cells. These aaDCs were capable of inducing IL-10 producing regulatory T effectors from naïve T cells whereas they modulated cytokine profile with suppressed production of IFN-γ and IL-17 by co-cultured memory T cells with attenuated proliferation. These aaDCs were shown to be superior to those generated using vitD3 alone in lupus patients.