Scientists at the University of Pennsylvania’s Perelman School of Medicine have discovered a new type of cell in human lungs.
Reporting in Nature, the scientists named the cells respiratory airway secretory cells (RASCs). The newly discovered cells have regenerative ability to replenish another group of cells implicated in chronic obstructive pulmonary disease (COPD), the team found, suggesting RASCs could open up a new way to treat COPD.
The Penn team discovered RASCs by performing single-cell RNA sequencing on lung tissue from healthy nonsmoker donors and found that the cells had a unique gene expression profile. The cells reside in airway branches, which interweave with the many tiny air sacs of the lung called alveoli, where air is exchanged.
The researchers soon identified RASCs as “secretory” cells because they produce proteins needed for the mucus lining the airway. A gene expression analysis revealed that RASCs and another type of progenitor cells called alveolar epithelial type 2 (AT2) shared some similarities. AT2 cells serve as stem cells for alveoli.
Besides their secretory function, RASCs can give rise to AT2 cells, the researchers showed. In patients with COPD and people who have smoking-induced lung injury, AT2 cells were altered in a way that suggested the dysfunction of RASCs’ differentiation to AT2 cells, the team found.
COPD is typically marked by damages to alveoli and the airways, most often from cigarette smoking or poor air quality. Several anti-inflammatory therapies have been approved to treat the disease. GlaxoSmithKline’s three-in-one inhaler, Trelegy Ellipta, for example, combines a corticosteroid, a long-acting muscarinic antagonist and a long-acting beta2 agonist. GSK co-funded the new Penn research.
In addition, novel anti-inflammatory biologics are emerging. Amgen and AstraZeneca have Tezspire (tezepelumab), an antibody that inhibits a cytokine called TSLP. The drug recently won an FDA approval to treat severe asthma, and the companies are also testing the drug in COPD.
Sanofi and Regeneron, marketer of asthma heavy hitter Dupixent, is working on an anti-IL-33 antibody, itepekimab, for COPD.
But dampening inflammation may only slow the progress of COPD, rather than stop or reverse it.
“Identifying new cell types, in particular new progenitor cells, that are injured in COPD could really accelerate the development of new treatments,” Maria Basil, M.D., Ph.D., the Penn study’s first author, said in a statement.
With the discovery of RASC and its role in alveoli, the Penn researchers suggest that restoring the normal RASC-to-AT2 differentiation or the normal RASC function in the lungs could be a new pathway to develop future COPD drugs.