Comparison of Tolerogenic Dendritic Cells Induced by Liver X Receptor Agonist from Bone Marrow-derived Cells and Natural Tolerogenic Dendritic Cells.

Background: Mouse dendritic cells (DCs) possess the tolerogenic potentiality after being induced by liver X receptor (LXR) agonist; while the characteristics and mechanisms of the induced DCs are still little known. Methods: Mouse bone marrow cells were pulsed with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) with or without LXR agonist-T0901317 for 7 days, or induced with lipopolysaccharide for 3 days. Cellular biomarkers, inducing ability of T cell proliferation and regulatory T cells (Treg) formation, and cytokines in culture supernatants were tested. OVA-specific CD4(+) T cells purified from BALB/c D011.10 RAG(-/-) mice were purified in Treg induction assay. NF-KB inhibitors and PI3K inhibitors were applied during cell culture. Natural tDCs (N-tDCs) isolated from mouse spleens were used as controls. Results: Compared with the N-tDCs, the morphology of T-tDCs (induced by T0901317 for 7 days) was similar to that of normal DCs but had slightly lower or moderate expression levels of CD80, CD86, and MEICIL The N-tDCs could significantly inhibit T cell proliferation, while T-tDCs lost their stimulatory effect on T cell viability. The co-treatment of T0901317 with NF-kappa B inhibitors or PI3K inhibitors propagated the inhibitory effect and resulted in significantly reduced T cell viability. The N-tDCs could induce the formation of Tregs, which was enhanced in the presence of TGF-beta; however, T-tDCs did not have this capability. T-tDCs secreted much higher levels of IL-10 than did the N-tDCs. Neither the T-tDCs nor the N-tDCs produced indoleamine 2,3-dioxygenase. Conclusions: Compared with N-tDCs, T-tDCs have inhibitory effects. But they should function via different modes, involving the NF-KB and PI3K signal pathways.