Iron can cause overactivity of special immune cells during an allergic asthma attack, causing excessive inflammation and narrowing of the airways, making breathing much more difficult.
A new study, in which experts from the Keck School of Medicine were also involved, examined the role iron plays in the function of the so-called innate lymphocytes of group 2 (also called ILC2 cells) and in the development of asthma. The results are published in the journal “Science Translational Medicine”.
ILC2 cells need iron to produce energy
The researchers carried out various tests with human cells and mouse models. It was shown that ILC2 cells require iron for a number of cellular processes and that iron plays an important role in the activation of immune cells.
In the body, iron enters cells by binding to a protein called transferrin. The new study used a detectable form of transferrin. The ILC2 cells were then activated with the help of an allergen.
Reduction of ILC2 activity
This showed that transferrin penetrated the cells. According to the researchers, this is evidence that iron was also absorbed. When the team then stopped the ILC2 cells from taking up transferrin (and iron), ILC2 activity decreased.
Additionally, the team tested the effects of deferiprone, a so-called iron chelator that is used to treat people with hemochromatosis (iron overload). The addition of deferiprone to cultured ILC2 reduced iron availability and therefore ILC2 activity.
Iron plays a key role
The experts then analyzed the so-called transcriptome of the ILC2 cells. It turned out that iron plays a key role in energy production.
The administration of an iron chelator in mice led to fewer lung infections and less hyperactivity of the respiratory tract compared to animals in a control group. In the absence of iron, the ILC2 have to adapt and produce energy in a different way, which is accompanied by reduced inflammation, the researchers explain.
Studies on 36 people with varying degrees of asthma also showed that blocking iron absorption reduces the activation of ILC2 cells.
The experts also found that some donors' cells had higher expression of a transferrin receptor, which caused the ILC2 cells to absorb more iron. According to experts, it is precisely this characteristic that correlates with more severe asthma.
New approaches to therapy?
This confirms a direct connection between iron intake and asthma in humans, the team reports. Overall, the results suggest a possible new therapy for allergic asthma that, in contrast to treatment with steroids, targets the cause of the disease.
“We cannot deprive a biological system of iron, which is an essential element for transporting oxygen in the body. “But limiting the availability of iron to immune cells in the lungs could reduce the exacerbation of asthma during an acute attack,” said study author Professor Dr. Omid Akbari in a press release.
This approach could also pave the way for the treatment of other immune-mediated and inflammatory lung diseases, and the study results could also open up new approaches to alleviating allergic diseases such as eczema, dermatitis, hay fever, rhinitis and food allergies, in which ILC2 cells also become overactive.
“Aside from steroids, there are few medications for asthma patients. Steroids, inhalers and tablets can control symptoms and keep patients alive, but they do not address the underlying pathophysiology of the disease. We hope that our research can ultimately provide a better solution,” adds Professor Dr. Akbari added. (as)
