Researchers at Karolinska Institutet in Sweden have studied which genes are expressed in overactive immune cells in mice with asthma-like inflammation of the airways.
Their results, which are published in the journal Immunity, suggest that the synthesis and breakdown of fats plays an important part in the process.
The job of the human immune system is to read our environment and react to potentially harmful substances.
In asthma, the immune system is overactive, causing inflammation in the lungs and symptoms such as coughing, wheezing and shortness of breath.
A kind of immune T cell called a Th2 plays a vital part in asthma-related inflammation, but the rarity of these cells and a lack of screening technology has made these cells hard to study in any detail.
Researchers at Karolinska Institutet have now used a highly sensitive technique called single-cell RNA sequencing to analyze which genes are active in individual T cells.
They monitored gene expression in T cells before and after exposure to the allergens in the lymph glands to the point of inflammation in the lungs.
They found that in the mouse lung, the T cells express a unique profile of hundreds of genes, many of which are linked to how the cells make and break down fat.
When they gave mice a drug to block fat metabolism, the lung inflammation decreased relative to controls.
“Our results suggest that fats can help to aggravate the T-cell activated inflammation in the lungs that is seen in asthma,” says the study’s corresponding author Jonathan Coquet, researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.
“We now plan to systematically test the importance of the hundreds of uniquely expressed genes in order to find those that can trigger or prevent the development of the disease.”
Another feature of the study was that when T cells reached the lungs from the lymph glands, they received signals that switched on the production of two powerful inflammatory substances: the cytokines interleukin 5 and 13.
These cytokines are responsible for many asthma symptoms such as respiratory tract inflammation, muscle contraction and mucus discharge.
“Our observation is that the T cells change a great deal over time, and seem to undergo a kind of reprogramming in the lungs that makes them highly inflammatory,” says Dr. Coquet.
The exact cause of asthma is unknown, and the causes may vary from person to person.
However, asthma is often the result of a strong response of the immune system to an allergen in the environment.
For example, exposure to an allergen in the environment, such as ragweed, may make your airways react strongly.
Other people exposed to the same allergen may not react at all, or their response may be different. The reason one person reacts to an exposure while others do not is not completely understood, though it may be partially explained by genes.
Asthma symptoms occur when the airways of the lungs narrow, which makes it more difficult to breathe.
This narrowing is usually caused by inflammation, which makes the airways swell and may cause the cells of the airway to make excess mucus. Bronchospasm, or tightening of the muscles around the airways, also makes the airways narrow and results in trouble breathing.
Over time, if asthma remains active, the airway walls can become thicker. The image below shows how airways narrow during asthma.
The immune system, and its role in asthma, is complex.
Genes seem to play a role in making some people more susceptible to asthma.
For example, some genes are involved in how your immune system responds to allergens.
These genes can cause a stronger reaction in your airways when certain substances in the air end up there.
The genes involved may be different in different people.
More information: Christopher Andrew Tibbitt et al, Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells, Immunity (2019).DOI: 10.1016/j.immuni.2019.05.014
Journal information: Immunity
Provided by Karolinska Institutet