Tregs and Immunosuppression in Environmental Illness!

 

      In the past several blogs, I have proposed that multiple chemical sensitivity may be due to the loss of Fox3p regulatory T cells  or Tregs which are negative regulators of inflammation. On one hand, several  studies over the past several years have demonstrated that the loss of immunosuppression from Tregs results in diseases like asthma or inflammatory bowel disease (Wang) But what about less common conditions like multiple chemical sensitivity (MCS) that seems to result in a "loss of tolerance"? Over the last six years, I have made a case for the aberrant signalling from the Nrf2 or AhR may also contribute to symptoms and Nrf2 activators which many are AhR ligands may be of benefit in relieving symptoms at least temporarily.  On the other hand, one author argued that patients exposed to less air pollution exhibited lower Tregs and that the increase or decrease of them could be useful in monitoring environmental disease. (Micovic)

     I found a few recent studies that are interesting as far as Treg suppression in relation to environmental disease. In one of these studies, Kohli found that a mixture of second hand smoke and ambient air pollution resulted in hypermethylation and decreased transcription of IFN-y and Fox3p Tregs. Passed studies show an association with a decrease of both of these proteins in asthma and allergic disease. Ambient air pollution, according to the author, is generally considered as "compounds that include polycyclic aromatic hydrocarbons (PAH), particulate matter that is less than 2.5 um (PM 2.5) , particulate matter less than 10um (PM10), carbon and ozone."

    Vallares has found that growth hormone (GH) stimulates T and B cell proliferation. In his study in autoimmune diabetes, he observed that consistent production of GH prevented the progression of pancreatic symptoms to overt autoimmune diabetes. This involved GH changing the cytokine environment and maintained a suppressor T cell (Treg) population.

    I have written several times about resveratrol, a phytochemical in wine, is an Nrf2 activator and might be a treatment for autoimmune disease like inflammatory bowel disease.  Recently Wang et al reported that resveratrol can inhibit inflammatory cytokines and relieve oxidative stress from a high-fat diet. Interestingly, resveratrol prevented the suppression of Tregs via the the aryl hydrocarbon receptor that is inhibited by high-fat diet. It seems that resveratrol not only stimulates Nrf2 but also acts through the AhR, and both of which I suspect could play a role in MCS. In addition, Busbee and Haniah write how AhR signalling may impact autoimmune disease by activating Fox3p Tregs and inhibiting or downregulating Th17. Haniah makes the comment that further study is needed but the AhR may prove to be a therapeutic strategy against autoimmune diseases.  Busbee notes that the AhR signals impact a number of genes, many of which I have discussed before and is present in a variety of tissue.  

       

For further reading:
Chemical Sensitivity and Th2 Autoimmune Disease: The Loss of Treg Cells As Referee!

T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis. Mucosal immunology (25 March 2015) by L. Wang, A. Ray, X. Jiang, et al. http://www.citeulike.org/user/kimberlykramer2015/article/13578157

Regulatory T cells (Tregs) monitoring in environmental diseases. Collegium antropologicum, Vol. 33, No. 3. (September 2009), pp. 743-746 by Vladimir Mićović, Bozo Vojniković, Aleksandar Bulog, et al. http://www.citeulike.org/user/kimberlykramer2015/article/6090770

Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children. Clinical epigenetics, Vol. 4, No. 1. (2012), doi:10.1186/1868-7083-4-17 by Arunima Kohli, Marco A. Garcia, Rachel L. Miller, et al. http://www.citeulike.org/user/kimberlykramer2015/article/13578755

ME/CFS as a Mitochondrial Disease Prohealth (26 April 2006) by David S. Bell, MD. http://www.prohealth.com/library/showarticle.cfm?libid=13611

 Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders. Nutrition reviews, Vol. 71, No. 6. (June 2013), pp. 353-369, doi:10.1111/nure.12024 by Philip B. Busbee, Michael Rouse, Mitzi Nagarkatti, Prakash S. Nagarkatti. http://www.citeulike.org/user/kimberlykramer2015/article/13407541

Toward understanding the role of aryl hydrocarbon receptor in the immune system: current progress and future trends. BioMed research international, Vol. 2014 (2014) by Hamza Hanieh. http://www.citeulike.org/user/kimberlykramer2015/article/13579639