title: Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis.
abstract: The immune response is normally controlled by regulatory T cells (Tregs). However, Treg deficits are found in autoimmune diseases, and therefore the induction of functional Tregs is considered a potential therapeutic approach for autoimmune disorders. The activation of the ligand-activated transcription factor aryl hydrocarbon receptor by 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or other ligands induces dendritic cells (DCs) that promote FoxP3(+) Treg differentiation. Here we report the use of nanoparticles (NPs) to coadminister ITE and a T-cell epitope from myelin oligodendrocyte glycoprotein (MOG)(35)(-55) to promote the generation of Tregs by DCs. NP-treated DCs displayed a tolerogenic phenotype and promoted the differentiation of Tregs in vitro. Moreover, NPs carrying ITE and MOG(35-55) expanded the FoxP3(+) Treg compartment and suppressed the development of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis. Thus, NPs are potential new tools to induce functional Tregs in autoimmune disorders.
authors: Center for Neurologic Diseases, Brigham and Women's Hospital,  Harvard Medical School, Boston, MA 02115.
authors: Ada
authors: A
authors: Yeste
authors: Meghan
authors: M
authors: Nadeau
authors: Evan J
authors: EJ
authors: Burns
authors: Howard L
authors: HL
authors: Weiner
authors: Francisco J
authors: FJ
authors: Quintana
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D000939:Epitopes / Q000737:chemistry; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D017930:Genes, Reporter; D006801:Humans; D007107:Immune System / Q000502:physiology; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008862:Microsomes, Liver / Q000378:metabolism; D009103:Multiple Sclerosis / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
chemical_list: D016207:Cytokines; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D008024:Ligands