Dexamethasone and Monophosphoryl Lipid A Induce a Distinctive Profile on Monocyte-Derived Dendritic Cells through Transcriptional Modulation of Genes Associated With Essential Processes of the Immune Response.

摘要: There is growing interest in the use of tolerogenic dendritic cells (tolDCs) as a potential target for immunotherapy. However, molecular bases that drive differentiation monocyte-derived DCs (moDCs) toward state are still poorly understood. Here, we studied transcriptional profile moDCs from healthy subjects, modulated with dexamethasone (Dex) and activated monophosphoryl lipid A (MPLA), referred to Dex-modulated MPLA-activated (DM-DCs), an approach identify regulators pathways associated induction properties tolDCs. We found DM-DCs exhibit distinctive compared untreated (DCs) MPLA-matured DCs. Differentially expressed genes downregulated by DM included MMP12, CD1c, IL-1B, FCER1A involved DC maturation/inflammation upregulated JAG1, MERTK, IL-10, IDO1 tolerance. Genes related chemotactic responses, cell-to-cell signaling interaction, fatty acid oxidation, metal homeostasis, free radical scavenging were strongly enriched, predicting activation alternative metabolic processes than those driven counterpart Furthermore, identified set regulated exclusively combined action Dex MPLA, which mainly control zinc homeostasis reactive oxygen species production. These data further support important role on DC-driven regulatory immune response. Thus, MPLA treatments modify gene expression inducing particular characterized tolerance-associated suppression inflammatory genes, conferring exert functions response modulation.