Regard sur l'épigénétique de l'asthme

Les modifications épigénétiques du génome ont un effet sur l'activité génétique des cellules., dont les cellules immunitaires. Un phénomène qui peut être à l'origine de maladies allergiques et d'asthme. L'épigénétique... Une interface entre les facteurs environnementaux et les maladies asthmatiques ?

The interface between environmental influences and asthma

Epigenetic changes to the genome have an effect on the gene activity of cells. Also, immune cells are not excluded from this, which can often be the cause of allergy-related diseases and asthma. Does epigenetics, therefore, form the interface between environmental factors and asthmatic diseases?

Immune cells produce a wide range of proinflammatory cytokines depending on cell type and degree of activation. One of the most potent cytokines is NfkB, which is also found in large quantities in asthmatics.

Epigenetics controls the activity of immune cells and thus the decision as to whether they are "normally" regulated or show excessive reactivities, as is the case in allergy sufferers. Due to epigenetic changes in the genome, cells can react very differently to stimuli. In pathophysiology, different phenotypes of diseases can also be explained.

Epigenetics influenced by diet

Epigenetics is defined as a change in gene expression without changing the DNA sequence. The main players responsible for epigenetics are generally considered to be methylation, histone modification and the action of non-coding mRNAs. Cells use all three mechanisms to control the activity of their genes. While some epigenetic changes have an inhibitory effect, others can also increase the activity of certain genes. In this way, epigenetics determines the development of an organism, as well as its growth or the development of the disease.

However, it is particularly interesting that epigenetic changes in genes can also be determined by environmental influences. A particularly effective environmental influence in this context is nutrition.

Epigenetic changes are partly environmental and hereditary

As shown in an experiment with agouti mice, the amount of methyl groups in food influences the degree of methylation of genes. For example, the mice changed the coat color depending on the methyl content of the food. In addition, it was found that the more methyl groups were present in their nutrition, the more inflammation the mice developed (Source 1).

In a further experiment with an asthma mouse model, those animals that had more methyl groups in their feed also developed an asthma-like disease much more frequently. The "predisposition" for asthma was also inherited through epigenetic changes from one generation to the next (Source 1).

What works with mice also seems to work with humans: In a twin study, for example, researchers demonstrated that 3-year-old twins have similar epigenetic changes in the genome. With increasing age, however, and the associated different lifestyles and diets, the picture of 50-year-old twins was clearly different. Here, there were very large differences in the number and type of epigenetic changes in the genome due to environmental factors (Source 2).

In addition, it is known from research that smoking during pregnancy can also lead to respiratory complications in the child. This is associated with a higher risk of asthma. It is also interesting to note that even if only the grandmother smoked, the newborn grandchild still has a significantly increased risk of developing secondary diseases since these are passed on at the level of epigenetics (Source 3).

Consequences for pathology and asthma therapy

Epigenetics also seems to explain the connection between asthma in children and their lives in city centers in the USA. Asthmatics also showed higher methylation rates and other active gene clusters than healthy people.

At the same time, epigenetics also offers opportunities to treat patients. The DNA is normally wrapped around histone octamers (Source 4). In asthmatics, these areas are often remarkably acetylated and thus active. However, this acetylation in certain gene regions can be used pharmacologically. The targeted use of de-acetylating drugs, for example, leads to a noticeable reduction in inflammation and ultimately asthma symptoms.

Sources:
1. Hollingsworth JW et al., J Clin Invest 2008 Oct;118(10): 3462-3469; doi: 10.1172/JCI34378 (partially retracted: J Clin Invest 2016;126(5):2012. doi:10.1172/JCI87742)
2. Fraga MF et al., PNAS 2005; 102(30): 10604-10609
3. Yu-Fen L et al., Chest 2005;127: 1232-1241
4. Wolffe AP & Hayes JJ. Nucleic Acids Res 1999 Feb 1;27(3): 711-720
5. HT 5 Epigenetics - the new frontier in asthma: Adcock I "The epigenetic clock", EAACI Congress 2019, Lisbon

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