Press Release

New discovery could help pave the way for better allergic asthma treatments

Leigh Hopper March 26, 2024
Research image shows inflammation in mouse lung cells on left and reduced inflammation from by treatment with Yoda1 on the right.

Activation of ILC2s causes inflammation in mouse lungs (left) but this is reduced by treatment with Yoda1 to stimulate Piezo1 channels (right). Photo/© 2024 Hurrell et al. Originally published in Journal of Experimental Medicine.

USC researchers working with mouse models and human cells have identified a potential new way to inhibit immune cells that drive the most common form of asthma.

The findings, which appear in the Journal of Experimental Medicine (JEM), point to a possible new therapeutic approach to reducing lung inflammation and treating allergic asthma most often caused by dust mites, pollen, animal dander and mold spores. 

Researchers at the Keck School of Medicine of USC discovered that a protein called Piezo1 prevents a type of immune cell in the lung from becoming hyperactivated by allergens.

In response to allergens, cells in the lungs called Type 2 innate lymphoid cells, also known as ILC2s, become activated and produce proinflammatory signals that drive the recruitment of other immune cells into the lungs. Unchecked, this can result in excessive inflammation and a tightening of the airways, making it difficult for asthma patients to breathe.

“Given the importance of ILC2s in allergic asthma, there is an urgent need to develop novel mechanism-based approaches to target these critical drivers of inflammation in the lungs,” says Omid Akbari, PhD, a professor of molecular microbiology and immunology at the Keck School of Medicine.

Akbari and his colleagues discovered that, when they are activated by an allergen, ILC2s also start to produce a protein called Piezo1 that can limit their ability to drive lung inflammation. Akbari’s team found that, in the absence of Piezo1, ILC2s from mice became more active than normal in response to allergenic signals, and the animals developed increased airway inflammation.

In contrast, treatment with a drug called Yoda1 that switches on Piezo1 channels reduced the activity of ILC2s, decreased airway inflammation, and alleviated the symptoms of allergen-exposed mice.

Finally, the researchers determined that human ILC2s also produce Piezo1, and so they tested the effects of Yoda1 on mice whose ILC2s had been replaced with human immune cells.

“Remarkably, treatment of these humanized mice with Yoda1 reduced airway hyperreactivity and lung inflammation, suggesting that Yoda1 may be used as a therapeutic tool to modulate ILC2 function and alleviate the symptoms associated with ILC2-dependent airway inflammation in humans,” Akbari said. “Future studies are therefore warranted to delineate the role of Piezo1 channels in human patients with asthma and to develop Piezo1-driven therapeutics for the treatment of allergic asthma pathogenesis.”

About the study

In addition to Omid Akbari, other study authors are Benjamin P. Hurrell, Stephen Shen, Xin Li, Yoshihiro Sakano, Mohammad Hossein Kazemi, Christine Quach, Pedram Shafiei-Jahani and Kei Sakano, all of the Keck School of Medicine of USC; and Homayon Ghiasi of the Cedars-Sinai Burns and Allen Research Institute.

The study was supported by National Institutes of Health Public Health Service grants R01 HL144790, R01 HL151493, R01 AI145813, and R01 HL159804.