IL13 Genomics: Elevating Th2 Immune Response

Do skin allergies or asthma run in your family? One genetic component to allergy susceptibility is IL-13, an immune system protein.

This quick overview explains how IL-13 can shift someone towards a higher Th2 immune response. I’ll cover the genetic variants in IL-13 that can elevate that response, and I end with natural supplements that can counteract this effect.

IL-13 and Th2 Activation:

Let me start by giving a brief overview of T cells and the immune system; then I’ll dive into specifics on IL-13.

A T cells is a type of white blood cells that matures in the thymus. T cells can mature and differentiate into different, distinct types of immune cells that have important functions in shaping the response of the immune system.

There are two main categories of T cells:  CD4+ “helper” T cells and CD8+ “killer” T cells.

The CD4+ helper T cells (abbreviated Th) are part of the adaptive immune response and activate other immune cells to mount a full response to pathogens.

The T helper cells are further divided into Th1 cells, Th2 cells, Th17, T regulatory cells, and more.

Th2 dominance

Th2 cells are what we are going to focus on here. The Th2 cells are vital to the way that the body responds to extracellular (outside the cell) pathogens, such as worm infections.

Th2 cells produce specific cytokines, called interleukin 4 (IL-4), interleukin 5, and interleukin 13 (IL-13). The cytokines produced by Th2 cells are able to trigger other immune cells to act (usually against parasitic worms).  Th2 cells can also cause B cells to proliferate and produce IgE antibodies.[ref]

Th2 cells produce IL-13, which acts on other immune cells including mast cells, basophils, and eosinophils.  When IL-13 activates mast cells or basophils, they can release histamine, serotonin, and other substances that can trigger blood vessels to dilate, stomach acid to be released, and intestinal peristalsis to increase. In the case of parasitic worms, this results in diarrhea to expel the worms.

When the Th2 system is overactive, allergies can occur with IgE antibodies produced for allergens.

Excessive Th2 activation, also called Th2 dominance, is linked to:[ref]

  • allergies
  • atopic dermatitis
  • asthma
  • histamine intolerance
  • chemical sensitivities
  • hyperactive immune response

What is interleukin 13 (IL-13)?

Interleukin 13 (IL-13) is a cytokine secreted by Th2 cells, mast cells, basophils, eosinophils, and natural killer T cells. It is considered to be a regulator of mucus hypersecretion (COPD), airway hyperresponsiveness (asthma), and IgE synthesis (allergies).[ref]

IL-13 has both immune system activation properties as well as ways that it acts as an anti-inflammatory.

As a cytokine, IL-13 is a signaling molecule that acts on receptors on cells.  The receptors that IL-13 binds to are the IL-4 alpha receptor (IL-4Ra) and the IL-13 receptor (IL-13R1). [ref]

Often when reading about IL-13 you will also see IL-4, another interleukin, mentioned. IL-4 and IL-13 are similar in structure and have some overlapping function. Together, they activate receptors that combine to create a specific response. Separately, IL-4 can activate different types of immune responses.  [ref]

On bronchial epithelial cells lining the lungs, IL-13 and IL-4 together stimulate the production of a lot of mucus.  This is an important way that we can get rid of pathogens in the lungs – trapping them in mucus and coughing them out.

IL-13 also promotes production of IgE by B cells.[ref]

Cell types and causes of IL-13 proliferation. For more details, read this open access article (CC 4.0): https://doi.org/10.3389/fphar.2019.01387

Asthma and IL-13:

Ashthma is a chronic inflammatory disorder in the lungs and airways. Researchers are now classifying asthma in two ways: T2-high asthma and T2-low asthma.  T2-high asthma has increased levels of Th2 cells, IgE, mast cells, eosinophils, and basophils. One research study explains “Patients with T2-high asthma have eosinophilia and other signs of type 2 inflammation including high levels of IL-4 and IL-13.” [ref]

Genetic variants in IL13 that increase the production are linked to increased risk of asthma.

Dust mites and airway inflammation:

House dust mites are microscopic little critters that live inside homes, eating dead skin cells. They thrive in humid, indoor air, but high altitude and very dry regions are pretty much dust-mite free. (Did you know that the average adult sheds 1.5 grams of dead skin cells each day?)[ref]

Dust mites are a really common airborne allergen, and they often trigger allergic asthma. IL-13 and IL-4 are elevated with repeated exposure to dust mites, and genetic variants in IL-13 are linked to increased risk of allergy or asthma from dust mites. [ref][ref]

IL-13 and aspirin exacerbated respiratory disease.

Taking aspirin or NSAIDS can trigger flares in about 10% of people with asthma. IL-13 plays a role in regulating the arachidonic acid pathway, downregulating PGE2. [ref]

IL-13 in the skin barrier:

A protein called filaggrin is integral to the structure of the outer layer of the skin. IL-13 can inhibit the production of filagrin, causing the skin barrier to be disrupted. Excessive IL-13, such as from genetic variants, can lead to atopic dermatitis or eczema. [ref]

IL-13 in cancer

IL-13 receptors are over-expressed in several types of solid cancers, and IL-13 levels can be elevated in certain cancers (pancreatic, esophageal). [ref]

IL-13 and Rheumatoid Arthritis:

It is all about balance with the Th1 and Th2 immune responses. IL-13 (and IL-4) have been shown to down-regulate the inflammatory processes that cause Rheumatoid arthritis.[ref]

Myocarditis, heart injuries, and IL-13:

Researchers have recently found that IL-13 is also secreted by a special type of cell called a type 2 innate lymphoid cell. In heart tissue, these type 2 innate lymphoid cells are an important part of the response to heart injuries, such as myocarditis or heart failure. Research seems to point to IL-13 having a positive role in younger hearts for exercise endurance, but in failing hearts, IL-13 over activation seems to “be the final straw”. [ref]


IL-13 Genotype Report

The genetic variants below are linked to an overactive response that may increase the relative risk of a number of allergy or asthma-type reactions. But these variants are common in the population because they also protect against parasite infections, which was a big survival advantage for our ancestors. [ref]

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IL13 gene:
encodes interleukin 13

Check your genetic data for rs20541 R130Q (23andMe v4, v5; AncestryDNA)

  • G/G: typical
  • A/G: higher IgE levels; higher risk of allergies, allergic rhinitis; increased risk of atopic dermatitis with childhood antibiotic use; increased risk of alopecia areata, increased risk of COPD
  • A/A:higher IgE levels; higher risk of allergies, allergic rhinitis (allergies that make your nose run)[ref][ref][ref]; increased risk of bullous pemphigoid [ref] increased risk of atopic dermatitis with childhood antibiotic use[ref] increased risk of alopecia areata[ref] increased risk of COPD[ref] increased dust mite allergies[ref]

Members: Your genotype for rs20541 is .

Check your genetic data for rs1800925 1112C>T (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: increase IgE levels; increased risk of asthma; increased risk of periodontitis, increased risk of COPD
  • T/T: increase IgE levels; increased risk of asthma; increased risk of periodontitis, increased risk of COPD [ref][ref][ref][ref][ref]

Members: Your genotype for rs1800925 is .

Check your genetic data for rs1295686 1923C>T (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: increased risk of asthma
  • T/T: increased risk of asthma[ref]

Members: Your genotype for rs1295686 is .

Check your genetic data for rs848 526C>A (23andMe v4, v5):

  • C/C: typical
  • A/C: increased risk of asthma,
  • A/A: increased risk of asthma, increased risk of alopecia areata[ref]

Members: Your genotype for rs848 is .


Lifehacks for high IL 13:

What can you do if you are genetically geared towards higher IL-13 levels?

First off, this is an advantage if you end up with parasitic worms :-). It is likely that these variants are common in the population due to the superpower they give you for fighting the helminths.

But in the modern world with hygiene and worm medicines, an excessive IL-13 response may tip you towards too much Th2 response – allergies, asthma, atopic dermatitis, etc.

Keep in mind that there may be times that you don’t want to inhibit IL-13, such as when having surgery or recovering from an injury.[ref]

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IL13 natural inhibitors:

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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 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.