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Dendritic Cells, Toll-Like Receptors, And Thyroid Autoimmunity

There are numerous cells which play a role in modulating the immune system in autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis.  In this blog post I’m going to focus on dendritic cells and toll-like receptors.  This admittedly will be a little more complex than many of the other articles and blog posts I’ve written, but every now and then I like to present some advanced information so that those people with autoimmune thyroid conditions can get a better understanding of what’s happening to their immune system.

Let’s start off by talking about what dendritic cells are.  Dendritic cells are one of the cells of your immune system, and they play a role in something called antigen presentation.  An antigen is a foreign molecule, and an example is pathogenic bacteria.  So for example, if someone has a bacterial infection, the dendritic cell will bind to the bacteria (antigen) and will then present it to the immune system.  And then of course the immune system will do everything it can to destroy the bacteria.

In addition to dendritic cells there are a few other antigen presenting cells.  These include macrophages and B lymphocytes.  Different antigen-presenting cells cause responses in different T cell populations (1).  In other words, while the goal of any antigen-presenting cell is to present an antigen to the immune system, dendritic cells will cause responses in different T cells than macrophages, which in turn will cause responses in different T cells than B lymphocytes.

What is A Major Histocompatibility Complex?

A major histocompatability complex (MCH) aids in allowing the immune system to recognize these antigens.  So for example, if there is pathogenic bacteria that invades the body, the MHC molecules are what actually bind to the proteins of these pathogens.  After doing this it displays them on the surface of the antigen presenting cell so that the appropriate T cells can recognize them, and of course these T cells then attempt to eradicate the bacteria.

You might wonder what specifically happens after the T cells recognize the antigens.  Of course we know that eventually the T cells will attempt to destroy the pathogen, but before this happens the T cell that binds to the MHC class II molecule is called a “naive” helper T cell.  If you have been reading my blog posts for awhile you might be familiar with Th1 and Th2 cells, and this naive helper T cell will become either a Th1 cell, a Th2 cell, a Th17 cell, or a regulatory T cell (2).  In a healthy immune system you want a balance of Th1 and Th2 cells, a large amount of regulatory T cells, and a low number of Th17 cells.  But with autoimmunity you commonly get an imbalance of the Th1 and Th2 pathways, along with an increase in Th17 cells and a decrease in regulatory T cells.

The Roll of Toll-Like Receptors                            

There are numerous studies which show that toll-like receptors play an essential role in the development of autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis (3) (4).  Toll-like receptors are a type of pattern recognition receptor, and these in turn recognize a wide range of something called pathogen-associated molecular patterns, also known as PAMPS (5).  PAMPs are found in pathogens such as viruses and bacteria.  An example of a PAMP is a lipopolysaccharide, which  are large molecules found in gram-negative bacteria, and I discussed this in greater detail in a past blog post I wrote entitled “What Are Lipopolysaccharides and How Can They Affect Thyroid Health?“.  These PAMPs are not normally found in the body of humans, and so they are immediately identified as being a foreign substance by the immune system.  There is also something called DAMPs, which stands for “damage-associated molecular patterns”.  Unlike PAMPs, which are associated with infections, DAMPs are usually associated with trauma.  Both PAMPs and DAMPs are involved in the inflammatory response.

Are Dendritic Cells Beneficial or Harmful?

Although we know that proinflammatory cytokines increase inflammation, and regulatory T cells help to decrease the autoimmune response, it’s not certain whether dendritic cells are beneficial or harmful in those with autoimmune conditions.  Although dendritic cells might play a role in triggering autoimmunity (6), more recent observations have shown that dendritic cells are important to ensure “immunological peace” by modulating regulatory T cells (7), which help to suppress autoimmunity.  The truth is that while we refer to some immune system cells as “bad”, or proinflammatory, while others as being “good”, or anti-inflammatory, all of these immune cells serve a purpose.  And so when you think about it this way, hopefully you’ll realize that no immune cell is inherently good or bad.

How Can We Modulate These Dendritic Cells?

In past articles and blog posts I’ve discussed things you can do to decrease proinflammatory cytokines and increase regulatory T cells, and I still recommend to focus on incorporating these factors while removing the autoimmune trigger.  However, there are a few studies which show that certain nutrients can modulate dendritic cells in a positive manner.  This includes vitamin D, which also can help to decrease proinflammatory cytokines and increase regulatory T cells.  And there is also evidence that the 1,25(OH)₂D₃-Vitamin D₃ complex can affect the maturation and migration of many dendritic cell subsets and help to regulate the immune system (8).  There is also evidence that vitamin A can modulate dendritic cells (9).

There is also evidence that polyphenols, which are found in fruits and vegetables, can have a positive effect on dendritic cells and shift the immune response towards tolerance or immune activation (10).  Another article specifically mentioned the polyphenols quercetin and piperine as influencing the maturation of dendritic cells and modulating the inflammatory response (11).  In other words, the authors claim that polyphenols can drive the dendritic cells towards an anti-inflammatory profile (11).

In summary, dendritic cells and toll-like receptors both play a role in modulating the immune system.  Dendritic cells present antigens such as bacteria to the immune system, which in turn will attempt to destroy the pathogen.  Something called a major histocompatability complex (MCH) aids in allowing the immune system to recognize these antigens.  Toll-like receptors are a type of pattern recognition receptor, and they play an important role in recognizing pathogen-associated molecular patterns, which are found in pathogens such as viruses and bacteria.  Some nutrients which can modulate the dendritic cells include vitamin D, vitamin A, and polyphenols such as quercetin and piperine.


 

1 Comment

  1. Tonya Scarborough says:

    I just want to say, thank you, so very much, for all of your articles. I’ve been following you on Facebook for a little over two years now. I found your blog when I was searching for answers and ways that I could heal myself naturally, right after I was diagnosed with hyperthyroidism. My Dr. told me that I would have to have my thyroid removed or radiated, for sure. I never was diagnosed with hashimoto’s or graves disease, and my endocrinologist never could tell me what had caused the attack. But common sense tells me that it was autoimmune related because I had all the other symptoms that suddenly began at the same time: joint pains, brain fog, weird skin rashes, etc. No Dr. would diagnose me with an autoimmune disorder because nothing was showing up on the labs, (except the hyperthyroidism) let alone tell me what I could do to actually heal myself. I scoured the internet for info. Your blog and Chris Kresser’s were like striking gold for me. Your articles gave me hope for a natural cure in the beginning, and have been very informative ever since. It’s hard to go with your gut when the dr.s are intimidating and scaring you into their approach. So, to have that support was so valuable to me. I ended up doing an autoimmune elimination + GAPS diet (despite the dr.’s telling me that I didn’t have an autoimmune disorder and that the symptoms were in my head), and I was off of the thyroid lowering meds in 2 months. I never had my thyroid removed or radiated and my levels went back to normal. Two years later, I have hardly any autoimmune symptoms as long as I eat properly and I can even have dairy again, which is a huge success for me! I hate to think of all the people who are sick with undiagnosed autoimmune conditions, and falling through the cracks, when really, some simple diet changes could save them from a lot of unnecessary and risky medical procedures, or even possibly save their life! Anyhow, I’m so grateful for all of your articles, and it is possible to heal yourself from an autoimmune disorder through diet, lifestyle, and environmental changes. Thank you!

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Natural Treatment Methods:
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Hypothyroidism Treatment
Hyperthyroidism Treatment
Natural Thyroid treatment


Conventional Treatment
Methods:
Radioactive Iodine
Thyroid Hormone