A novel heat-shock protein coinducer boosts stress protein Hsp70 to activate T cell regulation of inflammation in autoimmune arthritis.
OBJECTIVE
Stress proteins, such as members of the heat-shock protein (HSP) family, are up-regulated by cells in inflamed tissue and can be viewed functionally as "biomarkers" for the immune system to monitor inflammation. Exogenous administration of stress proteins has induced immunoregulation in various models of inflammation and has also been shown to be effective in clinical trials in humans. This study was undertaken to test the hypothesis that boosting of endogenous HSP expression can restore effective immunoregulation through T cells specific for stress proteins.


METHODS
Stress protein expression was manipulated in vivo and in vitro with a food component (carvacrol), and immune recognition of stress proteins was studied.


RESULTS
Carvacrol, a major compound in the oil of many Origanum species, had a notable capacity to coinduce cellular Hsp70 expression in vitro and, upon intragastric administration, in Peyer's patches of mice in vivo. As a consequence, carvacrol specifically promoted T cell recognition of endogenous Hsp70, as demonstrated in vitro by the activation of an Hsp70-specific T cell hybridoma and in vivo by amplified T cell responses to Hsp70. Carvacrol administration also increased the number of CD4+CD25+FoxP3+ T cells, systemically in the spleen and locally in the joint, and almost completely suppressed proteoglycan-induced experimental arthritis. Furthermore, protection against arthritis could be transferred with T cells isolated from carvacrol-fed mice.


CONCLUSIONS
These findings illustrate that a food component can boost protective T cell responses to a self stress protein and down-regulate inflammatory disease, i.e., that the immune system can respond to diet.
Wieten
Lotte
L
Institute of Infectious Diseases and Immunology, Utrecht University, 3584 CL Utrecht, The Netherlands.
van der Zee
Ruurd
R
Spiering
Rachel
R
Wagenaar-Hilbers
Josée
J
van Kooten
Peter
P
Broere
Femke
F
van Eden
Willem
W
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000081007:Cymenes; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology; D010581:Peyer's Patches / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D000081007:Cymenes; D018840:HSP70 Heat-Shock Proteins; D039821:Monoterpenes; D012333:RNA, Messenger; D016753:Interleukin-10; C073316:carvacrol