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Uncommon Lung Cell Regulates Immune Response

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uncommon lung cell

A type of lung cell acts as a sensor to regulate immune response.

An unusual and rarely-studied type of cell found in the lungs has been discovered to act somewhat like a sensor, linking together to central nervous system and the pulmonary system in order to regulate immune responses caused by stimuli in the environment.

A team of researchers, led by Xin Sun, who is a medical geneticist in the University of Wisconsin-Madison, published a research in the journal Science regarding pulmonary neuroendocrine cells, or PNECs. These cells are implicated in a number of lung diseases, such as asthma, pulmonary hypertension, sudden infant death syndrome, cystic fibrosis, and many more. Until now, the function of these cells in a live animal was unknown. The research by Sun and colleagues brings to light that PNECs are actually effective sensors that are seeded in the airways of many animals, which of course includes human beings.

The cells are around 1% of the total number of cells found in the airway epithelium, which are the cells that line the respiratory tract. Our conclusion is that they are capable of receiving, interpreting, and responding to environmental stimuli such as allergens or chemicals mixed with the air we breathe, says Sun.

Discovering the specific function of these cells would open new therapies for the pulmonary diseases in which these types of cells are implicated in.

Genetic Studies

The initial goal of Sun and her group was to actually find out the cause of a disease called congenital diaphragmatic hernia (CDH). This disease is a fairly common birth defect in which there is a hole in the newborn's diaphragm, which is the muscle that controls breathing. Because of the presence of this hole, organs from the abdomen slip into the chest. The hole can be surgically corrected, but most of the babies still do not survive. Those that do survive develop symptoms like asthma or pulmonary hypertension.

Preliminary results of the research led them to concentrate on two genes known as ROBO1 and ROBO2. These genes have been known to be associated with CDH, and by knocking out these genes, they were able to produce experimental CDH. To their surprise, PNECs were quite disorganized in the ROBO knockout mutants, whereas in healthy mice, PNECs were clustered. In the mutant, they don't cluster. They stay as solitary cells, and as single cells they are much more sensitive to the environment, says Sun.

Further investigation showed that dysfunction of the PNECs caused the hyperactive immune response that was seen in the lungs of the ROBO knockdown models.

At present, PNECs are the only type of cells seen in the airway lining that are connected to the central nervous system. Sun explains that these cells are likely to be distributed sensors, which gather information and stimuli from the environment, and then transmitting information to the brain. Conversely, these cells also receive information from the brain, in which they respond by upregulating their neuropeptides, which are small proteins that can potently regulate the immune response.
Disorders such as asthma are linked to a high level of neuropeptides. By revealing that PNECs function by regulating immune response through neuropeptide release, PNECs may as well be good targets to regulate, thereby preventing or lessening the symptoms of the disease.