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Mast Cells and Autoimmunity

Do you have more than one diagnosed health condition?

It’s not uncommon to see people with MCAS (mast cell activation syndrome), also having autoimmune conditions.

Mast cell involvement has been linked to many autoimmune conditions including:

Autoimmunity Progression

To survive, the human body must have a mechanism in place to distinguish between “self” and “non-self”. “Non-self” includes infectious pathogens, toxins, and other substances that may be perceived as a danger to the body.

Your body’s ability to recognize the difference allows you to mount an immune response to “non-self”, while at the same time recognizing that your own tissue is safe.

In autoimmunity, “self” and “non-self” get confused. It is normal for the immune system to respond to “non-self”.

How autoimmunity begins

For autoimmunity to occur, cross-reactivity must occur. Cross-reactivity is a situation where the immune system mistakes “self” for “non-self”—it sees a similarity in the molecular structure of the “non-self” to “self” and mistakenly mounts a response to “self".

Because of a similarity in molecular structure of the “non-self” (i.e. infection, food sensitivities...) with that of the body’s own tissue (“self”), this process is also referred to as molecular mimicry.

For cross-reactivity to occur, a number of factors have to be present such as dysbiosis (1) - aka an imbalance in your microbiome -, and leaky gut (2). You also need to have HLA genes (3, 4).

The combination of these factors leads to the immune responses associated with autoimmune conditions.

These responses involve both innate and adaptive immune involvement.

Mast cells are part of the innate immune system, so it is not surprising that they have a role to play. Research supports the involvement of mast cells in the progression of autoimmunity. (5).

Additionally, mast cell stabilizing drugs have been shown to reduce the severity of autoimmune encephalomyelitis (6) and multiple sclerosis (7).

Now that we know mast cells have a role in autoimmune progression, let’s look at how they are involved.

Mast Cells in Immune Regulation

Mast cells play a key role in immune regulation. They can stimulate or inhibit an immune response. They carry out this role by being in constant bi-directional communication with other immune cells. In layman’s language this means the cells are talking to one another.

There's a lot of signalling going on.

With both MCAS and autoimmunity, immune stimulation is occurring. Different immune cells are talking to one another in a way that promotes a heightened (or sensitized) immune response.

What are mast cells saying to other immune cells that contributes to autoimmune progression?

Mast cells release chemical mediators such as IL-6 (8) , TGF-β (9) , histamine (10) and PGD2 (11, 12) that communicate with the adaptive immune cells leading to Th17 or Th1/2 dominance associated with autoimmunity.

Wait... What? What are T-cells, and what do they have to do here?

T-cells are a type of immune cell that plays a key role in the inflammation associated with autoimmunity. These cells develop into T-helper cells depending on the conditions they are in.

The chemicals released by mast cells have a role in creating the conditions or environment that these cells develop in. With autoimmune conditions, we see that several of these helper cells are in higher ratios when compared to other immune cells than they would be in healthy individuals. These higher ratios are referred to as dominance, so Th17, Th1, or Th2 dominance tells you which type of T-helper cell is occurring in high levels.

Here are two such pathways (out of many) displayed in simplistic graphics:

Histamine, the most well understood mast cell mediator, has been shown to be involved in the progression of autoimmunity (13). Where there is histamine, there is mast cell involvement.

Understanding that mast cells and histamine play a role in autoimmune progression gives you a different perspective to consider in managing your symptoms. Could a low histamine, mast cell stabilization approach improve your autoimmune symptoms?

Steps to Take

  1. Are you using a dietary approach to help improve your autoimmune symptoms? Whether or not you are on an autoimmune protocol, adding a mast cell stabilizing approach is worth trying. Our cookbook is the only one around (as we write this) that does both! You can find it here.

  2. Enjoy all the amazing recipes and adapt as indicated in the book. There is so much deliciousness to be found in this book, regardless of what your health conditions are.

Up Next

Keep your eyes posted. We’ll be adding more to this conversation by looking at autoimmunity through the lens of sex and gender in our next blog post, coming up in two weeks.


Just making this connection for yourself between the histamine and autoimmune thing? Start getting a deeper understanding of just how histamine and mast cells may potentially be contributing to what's happening in your body.

Take our Master Class The Histamine Connection at no charge to you. You can join us for our next live session, or take a pre-recorded version. Or both! You'll find them both at this page. Register today to make that histamine connection for yourself, and learn how you can get started on building your safe haven with those foods you feature on your table.

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