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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 DO11.10 RAG-/- mice were purified in Treg induction assay. NF-κB 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 MHCII. The N-tDCs could significantly inhibit T cell proliferation, while T-tDCs lost their stimulatory effect on T cell viability. The cotreatment of T0901317 with NF-κB 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-β; 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-κB and PI3K signal pathways.
DOI: 10.7754/Clin.Lab.2015.150741
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