Chronic Inflammation & Autoimmune Risk – IL17

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... there are multiple types of T-helper cells that secrete different cytokines needed for different types of an immune response. 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 fungus 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 on a variety of different cell types, and activating the receptor, a number of different pro-inflammatory responses can happen.  For example, in a fungal infection, 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, lungs, and other epithelial cells such as 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 have shown to be 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 Genetic Variants:

There are genetic variations of 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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