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Regulatory T Cells and Thyroid Autoimmunity

When you think about it, the job that the immune system does in protecting us is simply incredible.  We are constantly being exposed to different pathogens, toxins, and food allergens, and our immune system does an amazing job of making sure these factors don’t cause us any harm, while at the same time differentiating self from non-self.  There are numerous regulatory mechanisms which help to maintain immune homeostasis and prevent the development of autoimmune thyroid conditions such as Graves’ Disease and Hashimoto’s Thyroiditis.  And one of the main components of the immune system which helps to prevent autoimmunity is the regulatory T cells.

Maintaining self-tolerance while at the same time mounting immune responses against pathogens is a complex process.  Regulatory T cells (Tregs) are widely regarded as the primary mediators of peripheral tolerance (1) [1].  Tregs originate in the thymus, although they also can derive from peripheral CD4+ T cells (2) [2].  A healthy immune system will have an abundance of these Tregs.  On the other hand, autoimmunity involves an imbalance of the Th1 and Th2 pathways, and also involves Th17 cells (3) [3].  As a result, when dealing with someone who has an autoimmune thyroid condition, the goal should be to increase the number and activity of the Tregs, while at the same time doing things to help suppress the Th17 cytokines.  Later in this post I’ll discuss some of the nutrients which can increase the number of Tregs and suppress the Th17 cells.

What is FoxP3?

FoxP3 is a transcription factor that is required for the development, maintenance, and function of Tregs (4) [1].  Deficiency or mutation in Foxp3 in humans and mice leads to a decrease in Tregs, which in turn leads to an early onset, highly aggressive and fatal autoimmune disease affecting various tissues (5) [4].  What’s important to understand is that Foxp3 plays an important role in the development and function of regulatory T cells, and both Foxp3 and Tregs are important in preventing the development of autoimmunity.

How To Increase The Number/Activity of Regulatory T Cells

Dr. Alex Vasquez is a chiropractor, naturopath, and osteopath who focuses on autoimmunity.  He is a contributing author of the Institute of Functional Medicine textbook, and he has written numerous journal articles.  In his book “Functional Immunology and Nutritional Immunomodulation” he discusses the nutritional induction of regulatory T cells by using certain nutrients.  What I’m going to do is list these nutrients, but I also have done my own research to see how these influence the Tregs, and of course will share these studies with you.

Vitamin A. Retinoic acid is a metabolite of vitamin A.  A few different studies show that retinoic acid induces Tregs in the presence of transforming growth factor Beta (6) [5] (7) [6].  The same studies reveal that retinoic acid can also inhibit the differentiation of Th17 cells, which as I mentioned earlier, play a big role in autoimmunity.  Some people with Graves’ Disease and Hashimoto’s Thyroiditis can benefit from taking 10,000 IU to 25,000 IU/day of vitamin A.  However, one does need to be cautious, as taking too high of a dosage of vitamin A for an extended period of time can lead to a toxicity.  And women who are pregnant, or are trying to become pregnant need to be especially cautious about taking high doses of vitamin A.  In the past I have written an article entitled “Vitamin A and Thyroid Health [7]“.

Vitamin D. I’ve written numerous articles and blog posts about the benefits of vitamin D.  25-OH vitamin D is what most doctors test for to determine whether someone has a vitamin D deficiency.  Although the lower end of most lab reference ranges for 25-OH vitamin D is 30 ng/mL, for optimal immune system health you want the levels to be at least 50 ng/mL.  Numerous studies show that vitamin D supplementation can help to increase the number of Tregs and therefore might help to prevent the development of autoimmune conditions (8) [8] (9) [9] (10) [10].

Probiotics. Many people take probiotics due to the benefits they have on the health of the gut.  Although this is true, let’s not forget that approximately 70% of the immune system is located in the gut.  As a result, taking probiotics can have a huge impact on the health of the immune system.  And certain strains of probiotics can increase regulatory T cells and help balance the Th1 and Th2 cytokines (11) [11] (12) [12].  If you read the second study you’ll notice that not all species have this effect, as both Lactobacillus reuteri and Lactobacillus casei induced the development of Treg cells, but not Lactobacillus plantarum.

Green Tea. Not too many people think of drinking green tea as a way to prevent autoimmunity.  Well, numerous studies show that the main ingredient of green tea, which is epigallocatechin-3-gallate (EGCG), interfered with the differentiation of Th1 and Th17 cells, and prevented IL-6 induced inhibition of Treg development (13) [13] (14) [14].  And so drinking green tea can increase the number of regulatory T cells and inhibit pro-inflammatory cytokines.  Even though the focus of this post is on autoimmunity, one very small clinical trial suggested that green tea can modulate circulating Tregs in the early stages of chronic lymphocytic leukemia and can potentially prevent the progression of the disease (15) [15].

Omega 3 Fatty Acids. I recommend for just about all of my patients to take omega 3 fatty acids, usually in the form of fish oils.  Omega 3 fatty acids can do a great job of controlling the inflammation, and there is also evidence that they can lead to an increased number of Tregs (16) [16] (17) [17] (18) [18].  However, this admittedly is controversial, as it also has been observed that DHA inhibited the suppressive effect of Tregs.

Lipoic Acid. Alpha lipoic acid can also help to increase the number of Treg cells while inhibiting Th1 and Th17 cells (19) [19].  Although I like alpha lipoic acid and do recommend it to some of my patients, in most cases I focus on giving some of the other nutrients listed here, and only have someone supplement with alpha lipoic acid if I feel it’s necessary.  However, one thing to keep in mind is that alpha lipoic acid can also increase glutathione levels (20) [20] (21) [21].  As I’ve discussed in other articles and blog posts, glutathione is a powerful antioxidant that has numerous functions, especially with regards to detoxification.

Turmeric and Resveratrol. I’ve spoken about both turmeric and resveratrol in past articles and blog posts.  These nutrients have numerous benefits, and there is also evidence that they can help to increase Tregs (22) [22] (23) [23].

While giving these nutrients can help to increase the number of Tregs, other factors most likely need to be addressed as well.  For example, if someone has a leaky gut due to consuming gluten, or exposure to a pathogen, then just giving nutrients to increase the number of Tregs won’t help much.  In other words, before one focuses on increasing the number of Tregs, it’s important to remove the factor which triggered the autoimmune response in the first place.  Once this has been accomplished then the person can take some of these nutrients to help suppress the autoimmune component and keep the immune system in balance.

Low Dose Naltrexone and Regulatory T Cells

For those who are familiar with Low Dose Naltrexone (LDN), this affects the opiate receptors in the brain, and this apparently results in an increase of regulatory T cells.  So this essentially is how LDN can help to modulate the immune system.  However, LDN does nothing to address the autoimmune trigger, which means that people will need to take LDN on a continuous basis.  And this is assuming that it works, as while LDN has helped many people, it isn’t always effective in suppressing the autoimmune component.

In summary, regulatory T cells help to keep the immune system in balance and prevent an autoimmune condition from developing.  People with Graves’ Disease and Hashimoto’s Thyroiditis typically have a lower number of Tregs, and so increasing these cells is important in order to suppress the autoimmune component of the condition.  Certain nutrients can help to accomplish this such as vitamin A, vitamin D, probiotics, and green tea.  However, as I have mentioned in previous blog posts and articles, one also needs to address the cause of these conditions in order to restore the person’s health back to normal.