Researchers at the Keck School of Medicine, University of Southern California, have discovered that the protein Piezo1 prevents a type of immune cell in the lung from becoming hyperactivated by allergens. The study, which was published in the Journal of Experimental Medicine, suggests that switching on Piezo1 could represent a new therapeutic approach to reducing lung inflammation and treating allergic asthma.
The study focused on Type 2 innate lymphoid cells (ILC2s), a type of immune cell that resides in the lungs, skin, and other tissues of the body. When activated by allergens, ILC2s produce proinflammatory signals that drive the recruitment of other immune cells into the lungs. This can result in excessive inflammation and a tightening of the airways, making it difficult for asthma patients to breathe.
The researchers found that, when ILC2s are activated by an allergen, they start to produce Piezo1, a protein that can limit their activity. Piezo1 forms channels in the outer membranes of cells that open in response to mechanical changes in the cell's environment, allowing calcium to enter the cell and change its activity.
In the absence of Piezo1, mouse ILC2s became more active than normal in response to allergenic signals, and the animals developed increased airway inflammation. Treatment with Piezo1 agonist Yoda1, which switches on Piezo1 channels, reduced the activity of ILC2s, decreased airway inflammation, and alleviated the symptoms of allergen-exposed mice.
The researchers also found that human ILC2s produce Piezo1, and treatment of mice whose ILC2s had been replaced with human immune cells with Yoda1 reduced airway hyperreactivity and lung inflammation. This suggests 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.