Treatment with Dexamethasone and Monophosphoryl Lipid A Removes Disease-Associated Transcriptional Signatures in Monocyte-Derived Dendritic Cells from Rheumatoid Arthritis Patients and Confers Tolerogenic Features.

摘要: Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated monophosphoryl lipid A (MPLA), referred to MPLA-tDCs, in terms gene expression, phenotype, cytokine profile, migratory properties, T cell-stimulatory capacity order explore their suitability cellular therapy. MPLA-tDCs derived displayed an anti-inflammatory profile reduced expression co-stimulatory molecules high IL-10/IL-12 ratio, but were capable migrating toward the lymphoid chemokines CXCL12 CCL19. These induced hyporesponsiveness autologous CD4+ specific synovial antigens vitro. Global transcriptome analysis confirmed a unique transcriptional revealed that RA-associated genes, which upregulated untreated DCs patients, returned levels healthy donor-derived after treatment MPLA. Thus, have develop tolerogenic features at well translational level, when MPLA, overcoming disease-related effects. Furthermore, ability impair cell responses validates potential RA.