title: Comparison of Tolerogenic Dendritic Cells Induced by Liver X Receptor Agonist from Bone Marrow-derived Cells and Natural Tolerogenic Dendritic Cells.
abstract: 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 co-treatment 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.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Xuyi
authors.initials: X
authors.lastname: Ma
authors.forename: Dan
authors.initials: D
authors.lastname: Song
authors.forename: Dong
authors.initials: D
authors.lastname: Xue
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: He
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D007108:Immune Tolerance; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D016328:NF-kappa B; D057093:Orphan Nuclear Receptors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides