UCSF study identifies cells responsible for cough reflex

When a mouthful of water goes through the wrong pipe and goes to the lungs instead of a healthy person's intestines, the person starts coughing uncontrollably. That's because their upper respiratory tract senses water and immediately sends a signal to their brain. A similar cough reflex is triggered in people with the following symptoms: acid reflux, when stomach acid reaches the throat. A new study by UCSF researchers could lead to prevention of pneumonia and treatment of certain types of chronic cough.

When a mouthful of water goes through the wrong pipe and goes to the lungs instead of a healthy person's intestines, the person starts coughing uncontrollably. That's because their upper respiratory tract senses water and immediately sends a signal to their brain. People with acid reflux experience the same cough reflex when acid from the stomach reaches the throat.

Now, scientists at the University of California, San Francisco have identified a rare type of cell that is involved in initiating these reactions. In a study published on April 19, 2024, scienceThey explain how cells called neuroendocrine cells in the larynx and trachea can sense water and acids in the upper respiratory tract and transmit information by releasing chemical messengers that activate nerves leading to the brain. accurately detailed.

This study may contribute to a better understanding of how these cough reflexes decrease with age and disease, and may lead to prevention of pneumonia and treatment of certain types of chronic cough.

This research provides a lot of insight into not only how our bodies protect our airways in this very surprising way, but also more broadly how our internal organs act as gatekeepers to the outside world. He will give it to you. ”

Dr. David Julius, lead author of the new paper, UCSF Professor and Professor of Physiology, and 2021 Nobel Prize Laureate in Physiology or Medicine

Neuroendocrine (NE) cells are found throughout the respiratory and digestive systems and have the dual functions of producing and releasing hormones, like endocrine cells, and sending and receiving electrical messages, like neurons .

cells react to water and acids

“We had some idea of ​​what these cells were doing in the lungs, but not in the upper airways,” said Laura Seeholzer, a UCSF postdoctoral fellow in Julius' lab who led the study. the doctor said. “The only reason we knew there were tumors in the larynx is because very rarely, people have neuroendocrine tumors in the larynx.”

Seeholzer isolated small and extremely rare NE cells from the upper and lower parts of the lungs, larynx, and trachea and developed a method to characterize the molecular details of the different cell groups. She studied what genes are active in each cell and what stimuli cause cells to release chemical signals. She found that, unlike NE cells in the lungs, NE cells found in the trachea and larynx do not respond to pressure changes. However, NE cells in the airways released signals in response to water and acid.

Seeholzer also used tissue isolated from mice to demonstrate how NE cells can transmit these messages directly to sensory neurons that connect to the brain. They then showed that activating NE cells in living mice caused the mice to swallow and cough, which are important reflexes for protecting the lungs. Conversely, when a mouse completely lacked her NE cells, it did not respond to airway water.

“We really wanted to understand the details of the mechanisms that drive these cells,” Julius said. “No one had shown before that these cells were talking to sensory neurons, so we wanted to trace the entire trajectory of the message.”

Potential treatments for chronic cough

Seeholzer said the new findings suggest that NE cells in the larynx and trachea are similar to taste buds and ear hair. They are not neurons themselves, but are connected to nerves that send sensory information to the brain.

“If you've ever had water aspiration or acid reflux, you know that both are incredibly painful, and you immediately cough, gag, and try to clear your airways,” Seeholzer said. To tell. “Now we have a better understanding of how the body causes it.”

As we age, the so-called cough reflex often becomes less sensitive, making older people and people with certain medical conditions more likely to aspirate fluid into their lungs and develop pneumonia. A new understanding of how NE cells are involved in the cough reflex may ultimately lead to ways to increase sensitivity and prevent aspiration. Targeting these cells could also treat the chronic cough associated with acid reflux in some people.

“Further research is needed to better understand how NE cells may change due to disease, smoking, and aging,” Seeholzer said. She is working with her UCSF clinicians on the next phase of this research.