What is terrible for the lungs could be helpful for the brain.

Asthma, a breathing disorder in which the airways narrow and become inflamed, can’t be described as pleasant.

However, those with asthma appear to have a lower risk of developing brain tumors than others. Researchers at St. Louis’ Washington University School of Medicine believe they’ve figured out why.

It all boils down to how T cells, a type of immune cell, behave. T cells become activated when a person – or a mouse – develops asthma. Researchers revealed that asthma leads T cells to act in a way that increases lung inflammation while inhibiting the growth of brain tumors in a new animal study. What is terrible for the lungs could be helpful for the brain.

The research, published in Nature Communications, reveals that reprogramming T cells in brain tumor patients to behave more like T cells in asthma patients could be a novel way to treat brain tumors.

“Of course, we’re not going to start inducing asthma in anyone; asthma can be a lethal disease. But what if we could trick the T cells into thinking they’re asthma T cells when they enter the brain, so they no longer support brain tumor formation and growth? These findings open the door to new kinds of therapies targeting T cells and their interactions with cells in the brain,” said David H. Gutmann, MD, PhD, Senior Author, the Donald O. Schnuck Family Professor of Neurology

Based on epidemiologic observations, the hypothesis that patients with inflammatory disorders like asthma or eczema are less likely to acquire brain tumors was initially presented more than 15 years ago. However, there was no obvious reason for the two very different diseases to be linked, and other scientists questioned if the link was genuine.

Gutmann specializes on neurofibromatosis (NF), a group of complex hereditary illnesses in which tumors grow on nerves in the brain and throughout the body. An optic pathway glioma is a form of brain tumor that can occur in children with NF type 1 (NF1). The optic nerves, which carry messages between the eyes and the brain, are home to these tumors.

More than five years ago, Gutmann, head of the Washington University NF Center, noticed an inverse relationship between asthma and brain tumors among his patients but didn’t know what to make of it. It wasn’t until more recent studies from his group revealed how important immune cells are in the development of optic pathway gliomas that he began to question if immune cells could explain the link between asthma and brain tumors.

Jit Chatterjee, PhD, a postdoctoral researcher and the paper’s primary author, took on the task of looking into the link. Chatterjee researched mice genetically modified to carry a mutation in their NF1 genes and generate optic pathway gliomas by 3 months of age with co-author Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine and director of the Division of Pulmonary & Critical Care Medicine.

Chatterjee subjected groups of mice to asthma-inducing irritants between the ages of 4 and 6 weeks, and treated a control group with saltwater for comparison. Then, at 3 and 6 months of age, he looked for optic pathway gliomas. These brain tumors did not occur in the asthmatic mice.

Further research found that generating asthma in tumor-prone mice alters the behavior of their T cells. When the mice acquired asthma, their T cells began secreting a protein known to asthma researchers as decorin.

Decorin is a disorder in the airways. It has an effect on the tissues that lining the airways, exacerbating asthma symptoms. However, Chatterjee and Gutmann discovered that decorin is advantageous in the brain. The protein then acts on immune cells known as microglia, preventing them from activating by interfering with the NFkappaB activation pathway. Microglia that are activated stimulate the growth and development of brain tumors.

Decorin or caffeic acid phenethyl ester (CAPE), a drug that blocks the NFkappaB activation pathway, were given to mice with NF1 mutations to protect them from developing optic pathway gliomas. The findings imply that inhibiting microglial activation could be a potentially beneficial therapeutic strategy for brain malignancies.

“The most exciting part of this is that it shows that there is a normal communication between T cells in the body and the cells in the brain that support optic pathway glioma formation and growth,” added Gutmann.

“The next step for us is to see whether this is also true for other kinds of brain tumors. We’re also investigating the role of eczema and early-childhood infections, because they both involve T cells. As we understand this communication between T cells and the cells that promote brain tumors better, we’ll start finding more opportunities to develop clever therapeutics to intervene in the process.”

Source: doi.org/10.1038/s41467-021-27455-6

Image Credit: Getty

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