Background: In a recent blog, we expressed an interest in a recent study that showed alterations in the distributions of suppressive T cells called Tregs which may influence environmental illness.(Micovic) According to the author, these cells are normally upregulated upon chronic inhalation of pollutants but in this case, the researcher noted a decrease in these suppressive cells. In other studies, a decrease in Foxp3 Tregs are often associated with autoimmune-like conditions. In addition, we also discussed a study the showed that particulate matter may alter "immunological footprints" and may lead to a autoimmune-like presentation. Also, regulatory Treg suppression plays a role in protection of striatal neurons and reductions of microglial neuroinflammation and alpha-synuclein and therefore, Tregs may play an important protective role in Parkinson's disease. It also suggests an explanation of how environmental exposures may contribute to PD and other neurodegenerative diseases. Catecholamines have been shown to downregulate the expression of Tregs and this is dependant on the expression of the dopamine D1-like receptors.
Other studies have revealed some insights into the relationship of Tregs and other proteing called heat shock proteins. Heat shock proteins are normally considered protective and often chaperone proteins during specific metabolic processes. De Zoeten recently showed that Tregs with HSP70 had more suppressive effects than those without. It was concluded that at least for this study of colitis, there was an important interaction with HSP70 and FoxP3+. Interestingly, a recent CFS study which is often co-morbid with colitis, demonstrated altered profiles of a number of heat shock proteins including HSP70 (Jammes) and suggested these proteins may be used as a biomarker for CFS. Wieten describes heat shock proteins as proteins that are normally upregulated in response to stress, including thermal and oxidative stress and inflammation and help prevent cellular damage by increasing the expression of anti-inflammatory T cells.
Weiten explains that by elevating the levels of heat shock proteins, an individual may be able to restore or increase their resistance to cellular stress. Weiten provides evidence that dietary phytonutrients can elevate levels of heat shock proteins. In his study, he found that several compounds found in food elevated HSP70 that elevated the expression of T cells. One such compound called carvacol is found in thyme and oregano. In other blogs, we have noted that the latter is associated with expression of PPAR-gamma which has anti-inflammatory properties. Hontecillas demonstrates in his research that PPAR-gamma can influence the activity of Tregs against inflammation. This seems to entail down-regulation of certain other T cells (Konturek) and as we have noted numerous times before, PPAR-gamma expression can be influenced by the expression of Nrf2.
Different studies have shown positive and negative consequences of exercise on environmental illnesses and this may be dependant on the levels of expression of a number of different proteins. In any case, it has been demonstrated that exercise positively influences the expression of HSP70.(Milne)Researchers from University of Alabama at Birmingham recently demonstrated that Treg cells in exercised mice increased cells with FoxP3+ and were better able to fascilitate suppression of inflammatory cytokines in an experimental model of murine asthama. In contrast, increasing age may negatively influence the expression of both Tregs and HSP70. Also, exposure to paraquat decreases expression of both HO-1 and HSP70 and increases oxidation of proteins. (Nakanishi) Muscle atrophy is often associated with aging and serious illness; the prevention of which can be influenced by the expression of HSP70. (Senf) Other studies show HSP are regulated through exercise-induced SIRT1 but interactions with HSP regulation is not the only way SIRT1 is involved in immune regulation. Reports now show that the dysregulation of SIRT1 leads to abnormal T cells responses and loss of tolerance and the development of autoimmunity. Zhang explains that while SIRT1 regulation is required for normal T cell activity, this responsibility does not involve maintaining Treg function or Th17 but does involve control of autoreactive T cells. In contrast, van Loosdregt mentions that use of HDAC inhibitors may be an alternative method for modulating FoxP3+ in Tregs. So it seems, the level of involvement of SIRT1 of Treg function is not at all clear and needs further study. In any case, the findings of the studies above, definitively demonstrate the importance of both Nrf2 and SIRT1 in regulation/dysregulation of immune function in a number of environmental illnesses.
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De Zoeten, E. F., Wang, L., Sai, H., Dillmann, W. H., and Hancock, W. W. (2009). Expression of hdac9 by t regulatory cells prevents colitis in mice. Gastroenterology. http://www.citeulike.org/user/HEIRS/article/6553713
Wieten, L., van der Zee, R., Goedemans, R., Sijtsma, J., Serafini, M., Lubsen, N. H., van Eden, W., and Broere, F. (2010). Hsp70 expression and induction as a readout for detection of immune modulatory components in food. Cell stress & chaperones, 15(1):25-37.
http://www.citeulike.org/user/HEIRS/article/4675555
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http://www.citeulike.org/group/7833/article/6553731
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