Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis

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 transcrip...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS Jg. 109; H. 28; S. 11270
Hauptverfasser: Yeste, Ada, Nadeau, Meghan, Burns, Evan J, Weiner, Howard L, Quintana, Francisco J
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 10.07.2012
Schlagworte:
Animals
Autoimmune Diseases - immunology
Cytokines - metabolism
Encephalomyelitis, Autoimmune, Experimental - immunology
Encephalomyelitis, Autoimmune, Experimental - therapy
Epitopes - chemistry
Epitopes, T-Lymphocyte - chemistry
Genes, Reporter
Humans
Immune System - physiology
Ligands
Mice
Mice, Inbred C57BL
Microscopy, Electron, Transmission - methods
Microsomes, Liver - metabolism
Multiple Sclerosis - metabolism
Myelin Sheath - immunology
Nanoparticles - chemistry
Nanotechnology - methods
T-Lymphocytes, Regulatory - cytology
ISSN:1091-6490, 1091-6490
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1091-6490
1091-6490
DOI:10.1073/pnas.1120611109