Asthma may reduce risk of brain tumors -- but how?
Mouse study IDs immune cells as link, points to potential therapeutic approaches

Date:
December 10, 2021
Source:
Washington University School of Medicine
Summary:
Asthma has been associated with a lowered risk of brain tumors,
and researchers now think they know why: Immune cells activated
under conditions of asthma are less able to promote the growth of
brain tumors.

The findings could lead to new therapeutic approaches.



FULL STORY ========================================================================== There's not much good that can be said about asthma, a breathing disease
in which the airways become narrowed and inflamed. But there's this:
People with asthma seem to be less likely to develop brain tumors than
others. And now, researchers at Washington University School of Medicine
in St. Louis believe they have discovered why.


==========================================================================
It comes down to the behavior of T cells, a type of immune cell. When
a person -- or a mouse -- develops asthma, their T cells become
activated. In a new mouse study, researchers discovered that asthma
causes the T cells to behave in a way that induces lung inflammation
but prevents the growth of brain tumors.

What's bad news for the airways may be good news for the brain.

The findings, available online in Nature Communications, suggest that reprogramming T cells in brain tumor patients to act more like T cells
in asthma patients could be a new approach to treating brain tumors.

"Of course, we're not going to start inducing asthma in anyone; asthma
can be a lethal disease," said senior author David H. Gutmann, MD, PhD,
the Donald O.

Schnuck Family Professor of Neurology. "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." The idea that people
with inflammatory diseases, such as asthma or eczema, are less prone
to developing brain tumors was first proposed more than 15 years ago,
based on epidemiologic observations. But there was no obvious reason
why the two very different kinds of diseases would be linked, and some scientists questioned whether the association was real.

Gutmann is an expert on neurofibromatosis (NF), a set of complex
genetic disorders that cause tumors to grow on nerves in the brain and throughout the body. Children with NF type 1 (NF1) can develop a kind
of brain tumor known as an optic pathway glioma. These tumors grow
within the optic nerves, which carries messages between the eyes and
the brain. Gutmann, director of the Washington University NF Center,
noted an inverse association between asthma and brain tumors among
his patients more than five years ago but didn't know what to make of
it. It wasn't until more recent studies from his lab began to reveal the crucial role that immune cells play in the development of optic pathway
gliomas that he began to wonder whether immune cells could account for
the association between asthma and brain tumors.

Jit Chatterjee, PhD, a postdoctoral researcher and the paper's first
author, took on the challenge of investigating the association. Working
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 studied mice genetically modified to carry a
mutation in their NF1 genes and form optic pathway gliomas by 3 months
of age.

Chatterjee exposed groups of mice to irritants that induce asthma at
age 4 weeks to 6 weeks, and treated a control group with saltwater
for comparison.

Then, he checked for optic pathway gliomas at 3 months and 6 months of
age. The mice with asthma did not form these brain tumors.

Further experiments revealed that inducing asthma in tumor-prone mice
changes the behavior of their T cells. After the mice developed asthma,
their T cells began secreting a protein called decorin that is well-known
to asthma researchers.

In the airways, decorin is a problem. It acts on the tissues that line the airways and exacerbates asthma symptoms. But in the brain, Chatterjee
and Gutmann discovered, decorin is beneficial. There, the protein
acts on immune cells known as microglia and blocks their activation by interfering with the NFkappaB activation pathway. Activated microglia
promote the growth and development of brain tumors.

Treatment with either decorin or caffeic acid phenethyl ester (CAPE),
a compound that inhibits the NFkappaB activation pathway, protected mice
with NF1mutations from developing optic pathway gliomas. The findings
suggest that blocking microglial activation may be a potentially useful therapeutic approach for brain tumors.

"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,"
said Gutmann, who is also a professor of genetics, of neurosurgery
and of pediatrics. "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." ========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Tamara
Bhandari. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jit Chatterjee, Shilpa Sanapala, Olivia Cobb, Alice Bewley,
Andrea K.

Goldstein, Elizabeth Cordell, Xia Ge, Joel R. Garbow, Michael J.

Holtzman, David H. Gutmann. Asthma reduces glioma formation
by T cell decorin-mediated inhibition of microglia. Nature
Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-27455-6 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211210155045.htm

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