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

Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11270-5. doi: 10.1073/pnas.1120611109. Epub 2012 Jun 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Cytokines
  • Epitopes
  • Epitopes, T-Lymphocyte
  • Ligands