An uncommon and little-studied type of cell in the lungs has been found to act like a sensor, linking the pulmonary and central nervous systems to regulate immune response in reaction to environmental cues.
The cells, known as pulmonary neuroendocrine cells or PNECs, are implicated in a wide range of human lung diseases, including asthma, pulmonary hypertension, cystic fibrosis and sudden infant death syndrome, among others.
Pulmonary neuroendocrine cells (red) are rare cells found in clusters along the mammalian airway, where they act as sensors, sending information to the central nervous system. These clusters are found interspersed among other airway epithelial cells (green). The cells, whose function was previously unknown, have been found by a group led by medical geneticist Xin Sun to sense environmental stimuli and report to the nervous system to orchestrate an immune response.
Credit: Leah Nantie
Until now, their function in a live animal was unknown. A team led by University of Wisconsin-Madison medical geneticist Xin Sun reports in the current (Jan. 7) issue of the journal Science that PNECs are effective sensors seeded in the airway of many animals, including humans.
"These cells make up less than one percent of the cells in the airway epithelium," the layer of cells that lines the respiratory tract, explains Sun. "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."
Discovering the function of the cells may provide new therapeutic avenues for a wide range of serious diseases of the pulmonary system.
Sun and her group initially set out to find the underlying cause of congenital diaphragmatic hernia (CDH), a fairly common birth defect where a hole in a newborn's diaphragm, the muscle that controls breathing, lets organs from the abdomen slip into the chest. The deformed diaphragm can be repaired surgically, but many of the babies still die. Those that survive can have symptoms similar to asthma or pulmonary hypertension.
The Wisconsin group homed in on a pair of genes known as ROBO1 and ROBO2. Mutations in the genes had previously been implicated in CDH. By knocking out ROBO genes in mice, Sun and her colleagues were able to mimic CDH. Unexpectedly, they also discovered that PNECs were disorganized in the ROBO mutants. In a healthy mouse, PNECs mostly form clusters of cells. "In the mutant, they don't cluster," says Sun. "They stay as solitary cells, and as single cells they are much more sensitive to the environment."
The team went on to show that defects in the PNECs caused the hyperactive immune response in the ROBO mutant lungs.
PNECs are the only known cells in the airway lining that are linked to the nervous system. It seems, explains Sun, that they are basically distributed sensors, gathering information from the air and relaying it to the brain. Interestingly, the same cells also receive processed signals back from the brain to amp up their secretion of neuropeptides, which are small protein molecules that are potent regulators of the immune response.
Disorders of the immune system like asthma are associated with increased expression of neuropeptides. Showing that PNECs play a role in regulating host response through the release of neuropeptides suggests that it may be possible to devise ways of regulating them to prevent or ameliorate disease, Sun says.
Sun is a professor of medical genetics in the Laboratory of Genetics of the UW School of Medicine and Public Health. Contributing to the work were Kelsey Branchfield, Leah Nantie, Jamie Verheyden, Pengfei Sui and Mark Weinhold, all of UW-Madison. The new study was supported by awards from the American Heart Association, the National Institutes of Health and, at the campus level, by the Wisconsin Partnership Program and a Romnes Faculty Fellowship. Romnes Fellowships are awarded by the UW-Madison Office of the Vice Chancellor for Research and Graduate Education with funding from the Wisconsin Alumni Research Foundation.
CONTACT: Xin Sun, (608) 265-5405, email@example.com
DOWNLOAD PHOTOS: https:/
Terry Devitt, (608) 262-8282, firstname.lastname@example.org
Xin Sun | EurekAlert!
Tracking movement of immune cells identifies key first steps in inflammatory arthritis
23.01.2017 | Massachusetts General Hospital
Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Health and Medicine
23.01.2017 | Physics and Astronomy
23.01.2017 | Process Engineering