Cell by Cell, Researchers Plot Landscape of the Lung to Aid Asthma Research

European researchers said Monday they have mapped the human lung on a single-cell level, differentiating cell types between patients with asthma and those without, including the discovery of a new cell state that produces mucus in asthma.

The anatomical map, published in Nature Medicine, shows the differences between healthy airways and asthmatic airways and identifies how cells in the lung communicate. This understanding could lead to finding new drug targets for treating asthma, the researchers said.

One symptom of asthma is an overproduction of mucus, but not all of the cells responsible for this were previously known. In this study, researchers used single-cell transcriptomics to map upper and lower airways and lung parenchyma in healthy lungs, and lower airways in lungs affected by asthma.

They discovered location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cell hyperplasia stems from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. In diseased lungs that have been remodeled by asthma, researchers discovered pathogenic effector type 2 helper T cells (Th2), and found evidence for type 2 cytokines in maintaining the altered epithelial cell states.

Examining intercellular communications in both healthy and diseased airway walls showed a loss of structural cell communication and a rise in inflammatory Th2 cell interactions, which send the vast majority of cellular signals in asthma.

“We already knew that inflammatory Th2 cells played a role in asthma, but only now do we see how great that influence is,” said Martijn Nawijn, PhD, a senior author from University Medical Center Groningen, in a statement. “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.”

Location is important for the lung cells, as cells in different areas have very different cellular activities. This has further implications for studying drug targets and designing drug trials, the researchers said.

The research was conducted by the Wellcome Sanger Institute, University Medical Center Groningen, Open Targets, and GlaxoSmithKline.

Reference

Vieira Braga FA, Kar G, Berg M, et al. A cellular census of human lungs identifies novel cell states in health and in asthma [published online June 17, 2019]. Nat Med. doi: 10.1038/s41591-019-0468-5.