Tolerogenic dendritic cells that inhibit autoimmune arthritis can be induced by a combination of carvacrol and thermal stress

PLoS One. 2012;7(9):e46336. doi: 10.1371/journal.pone.0046336. Epub 2012 Sep 25.

Abstract

Tolerogenic dendritic cells (DCs) can induce regulatory T cells and dampen pathogenic T cell responses. Therefore, they are possible therapeutic targets in autoimmune diseases. In this study we investigated whether mouse tolerogenic DCs are induced by the phytonutrient carvacrol, a molecule with known anti-inflammatory properties, in combination with a physiological stress. We show that treatment of DCs with carvacrol and thermal stress led to the mRNA expression of both pro- and anti-inflammatory mediators. Interestingly, treated DCs with this mixed gene expression profile had a reduced ability to activate pro-inflammatory T cells. Furthermore, these DCs increased the proportion of FoxP3(+) regulatory T cells. In vivo, prophylactic injection of carvacrol-thermal stress treated DCs pulsed with the disease inducing antigen was able to suppress disease in a mouse model of arthritis. These findings suggest that treatment of mouse bone marrow derived DCs with carvacrol and thermal stress induce a functionally tolerogenic DC that can suppress autoimmune arthritis. Herewith carvacrol seems to offer novel opportunities for the development of a dietary based intervention in chronic inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / therapy*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy*
  • Cymenes
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology*
  • Female
  • Flow Cytometry
  • Mice
  • Mice, Inbred BALB C
  • Monoterpenes / pharmacology*
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Temperature

Substances

  • Cymenes
  • Monoterpenes
  • carvacrol

Grants and funding

Innovatiegerichte Onderzoeksprogramma (IOP) Genomics: IGE07004 (http://www.agentschapnl.nl/en) European Union FP7 TOLERAGE: HEALTH-F4-2008-20215 (http://www.tolerage.eu/) Dutch Arthritis Association (http://www.reumafonds.nl/informatie-voor-doelgroepen/professionals/research-funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.