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).  IL-17 is important in eliminating bacteria and fungus both inside cells and outside cells.[ref]

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

IL-17 is implicated in increasing the risk for several autoimmune diseases including psoriasis and asthma. IL-17 is mainly active in the skin and mucosal regions (lungs, gastrointestinal tract), 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), 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-17A Genetic Variants:

There are genetic variations of IL-17A 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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