DENVER - Airway hyperresponsiveness, a feature commonly found in diseases such as asthma, chronic obstructive pulmonary disease and environmental lung diseases, may be linked to a lack of gamma/delta T cells in the lungs National Jewish Medical and Research Center scientists write in today’s Nature Medicine.
The research sheds light on a previously unknown immune system mechanism that depends on gamma/delta T cells, found in small numbers in the lungs, to stop airway constriction independently of other T cells.
“Gamma/delta T cells in the lungs are a small population, but have a big impact,” said Michael Lahn, M.D., a National Jewish Fellow and an author of the study. Dr. Lahn and Arihiko Kanehiro, M.D., both National Jewish Fellows, are principal authors of the study.
The research found that gamma/delta T cells ensure that airways are relaxed each time they are exposed to stimuli, such as a protein used to create a model of asthma in mice. Airways of mice without gamma/delta T cells in their lungs constricted significantly when exposed to airway stimuli, according to the research. In comparison, mice deficient in another type of T cell did not have airway constriction, leading the scientists to judge that gamma/delta T cells have a suppressive effect on airway hyperresponsiveness.
“This was a very surprising finding,” Dr. Lahn said. “Even more surprising was that everything implicated in causing airway hyperresponsiveness in the past was not detected, such as evidence of inflammation.”
Found in already limited numbers in the lungs of people without asthma, gamma/delta T cells are observed in even smaller numbers in the lungs of people with the lung disease. Whether reduced gamma/delta T cells in these patients increase the likelihood for wheezing needs to be addressed with further research, Dr. Lahn said.
“Gamma/delta T cells are essential in day-to-day regulation of the airways,” he said. “And they control, in a very potent way, stressful events anytime the lungs or the airways get exposed to airway stimuli.”
In the future, as scientists learn more about how gamma/delta T cells work and interact with other T cells, it’s possible that people with asthma and other lung diseases could use medication to boost their level of gamma/delta T cells, which would lower airway hyperresponsiveness.
The labs of Willi Born, Ph.D., Erwin Gelfand, M.D. and Rebecca O’Brien, Ph.D., collaborated in this research. Dr. Lahn is a Fellow in Dr. Born’s lab; Dr. Kanehiro is a Fellow in Dr. Gelfand’s lab.
The National Institutes of Health and the U.S. Environmental Protection Agency funded this study.
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