Tolerogenic dendritic cells that inhibit autoimmune arthritis can be induced by a combination of carvacrol and thermal stress.
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.
Department of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands.
Rachel
R
Spiering
Ruurd
R
van der Zee
Josée
J
Wagenaar
Dimos
D
Kapetis
Francesca
F
Zolezzi
Willem
W
van Eden
Femke
F
Broere
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D000081007:Cymenes; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D013696:Temperature
D000081007:Cymenes; D039821:Monoterpenes; C073316:carvacrol