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Chronic Inflammation & Autoimmune Risk: IL17 gene variants

Inflammation can be blamed for everything from heart disease to mood disorders to obesity. Yet, how does this somewhat nebulous idea of too much inflammation tie into our genes? It seems that some people have a more sensitive immune system and are more prone to inflammatory reactions.

Inflammation and IL-17:

Interleukin-17 (IL-17A gene) is a pro-inflammatory cytokine produced by T-helper cells. It is part of our immune system — necessary in times of injury or pathogenic infection but problematic if overactive.[ref]

A quick overview of the immune system:

Our immune system’s composition includes many different parts and is responsible both for fighting off foreign pathogens (bacteria, viruses, etc.) and clearing out old or defective cells in the body. Thus, the immune system needs to recognize which cells are pathogens and which cells are part of the body. T-cells, also called T-lymphocytes, are a type of white blood cell that seeks out and destroys pathogens. There are two types of T-cells, T-helper cells and T-effector cells. T helper cells help to organize the immune response against a pathogen.

Going a little deeper here… multiple types of T-helper cells secrete different cytokines needed for different types of immune responses. One of the T-helper cells is Th17, which secretes the inflammatory cytokine IL-17 (interleukin-17).[ref]

IL-17 in Inflammation and Autoimmunity:

IL-17, produced by Th17, is important in eliminating bacteria and fungi both inside cells and outside cells.[ref]

IL-17 has six different subtypes, from IL-17A to IL-17F. As inflammatory signaling molecules, both IL17A and F act on the same receptor (IL-17R).

The IL-17 receptor is found in a variety of different cell types, and by activating the receptor, a number of different pro-inflammatory responses can happen. For example, in fungal infections, IL17 signaling can directly increase ROS production to fight off the fungus.[ref]

One of the main roles of IL17 is to protect ‘barrier integrity’ – the body’s front line against outside invaders. This means that the IL-17 receptor is found in skin tissue, mucosal tissue, the lungs, and other epithelial cells, such as those lining the intestines. One role of IL-17 is to maintain the tight junctions between the epithelial cells, and another action is to induce the release of antimicrobial chemokines in response to pathogens.[ref]

Increased risk for autoimmune diseases:

The flip side of this awesome fighter of pathogens is that IL-17 can cause damage to your tissues if it is too active. Research shows that IL-17 genetic variants can be a causative factor in several different autoimmune diseases.[ref][ref]

IL-17 is implicated in increasing the risk for several autoimmune diseases, including psoriasis, Hashimoto’s, and asthma. As mentioned above, IL-17 is mainly active in the epithelial and mucosal regions (lungs, gastrointestinal tract, skin), which explains its role in psoriasis, asthma, and other related conditions.

Genetic variants that increase the body’s production of IL-17A are a risk factor for inflammatory bowel disease (IBD), psoriasis, rheumatoid arthritis, bronchitis severity, gastric cancer, and more.

IL-17A is also implicated in celiac disease, with increased expression of IL-17A found in the intestinal mucosa of Celiac patients. Gluten sensitivity, though, was not found to increase IL-17A.[ref][ref]

IL-17 Genotype Report

There are genetic variations in IL-17 causing it to be either more active than normal (increasing risk of autoimmune/inflammatory conditions) – OR – less active than normal (protective against autoimmune/inflammatory conditions).

As is almost always the case, diet and environment interact with genetics in the development of chronic diseases. Thus, just carrying the variant doesn’t cause inflammatory diseases, per se, but instead increases the susceptibility to them in conjunction with other factors.

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Lifehacks for decreasing high IL-17

If you have an increased IL-17 response that is exacerbating an inflammatory condition, you may want to look into natural ways to decrease IL17.

Keep in mind that tamping down IL-17 may not be a good idea if you’re also trying to fight off a pathogen. Talk with your doctor if you have any questions about supplements and their interactions with medications.

Dietary Changes that Impact IL-17:

Sprinkle on the spices: Ursolic acid, which is a natural carboxylic acid found in rosemary and thyme, is a strong inhibitor of IL-17.[ref] It is also a component of rosemary extract, which was traditionally used for treating rashes, wounds, dyspepsia, etc.[ref]

Vitamin C appears to upregulate IL-17, which may be good when fighting off a pathogen.[ref]

Apples contain high concentrations of procyanidin B1 and B2, which inhibit the production of IL17.[ref]

Naringenin in citrus fruits, like grapefruit, is a natural inhibitor of IL17.[ref]

6 Natural supplements that decrease IL-17:

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.