Detailed lung cell map uncovers new pieces of the asthma puzzle

Considering how common asthma is, it's rather surprising that we don't know all that much about how the condition works. Now, as part of the Human Cell Atlas initiative researchers have mapped the different types of cells in the lungs, and spotted some crucial new differences between healthy and asthma-affected airways that could inspire some new drug targets.

The researchers studied more than 36,000 individual cells, from the nasal area and three different parts of the lung, in samples taken from 17 people without asthma. These were analyzed to determine which cell types were where, and which genes were active in each cell.

Using this as a baseline, the team then performed the same examinations of cells taken from six patients with asthma, and compared the two groups. That allowed them to identify the cellular differences between healthy and asthmatic lungs, and even discover a new cell state that contributes to the symptoms of the condition.

One of the key discoveries was a problem with how airway cells communicate with each other. Normally, a range of cells work together to keep airways functioning, but in the new cellular census, the team found that inflammatory immune cells called type 2 T helper (Th2) cells were overactive. That means they readily become inflamed, narrowing the airways and causing the breathing difficulties characteristic of an asthma attack.

"We already knew that inflammatory Th2 cells played a role in asthma, but only now do we see how great that influence is," says Martijn Nawijn, senior author of the study. "In normal people, all kinds of cells communicate with each other in order to keep the airways functioning well. But in asthma patients, almost all of those interactions are lost. Instead of a network of interactions, in asthma the inflammatory cells seem to completely dominate the communication in the airways."

An overproduction of mucus is another symptom of asthma, and the team also discovered a new cell state, called the muco-ciliated state, in the lower airways of asthma patients. The third main lesson was that cells in different parts of the lung showed very different activities.

Altogether, these findings could lead to new drug targets for asthma treatment. That might include developing drugs that prevent cells from responding to the overactive inflammatory signals, which in turn would keep the airways open.

"As part of the Human Cell Atlas initiative, we have created the first comprehensive cellular map of the lungs," says Sarah Teichmann, senior author of the study. "Our large-scale, open access data reveals the activity of different cells, their communication pathways and locations. The lung cell atlas will provide a great resource for further lung research and we hope that it will enable the identification of potential new therapeutic targets for asthma relief."

The research was published in the journal Nature Medicine.

Source: Wellcome Sanger Institute