Rare immune cells offer new hope for treating acute respiratory distress syndrome

Basophils, a type of white blood cell, promote recovery from acute respiratory distress syndrome (ARDS) in mice, according to researchers at Science Tokyo. In a mouse model of ARDS, basophils were found to release interleukin-4 (IL-4), which suppresses inflammatory neutrophils in the lungs during the recovery stage. The study suggests that targeting the basophil–IL-4–neutrophil pathway could offer a new therapeutic approach for ARDS, a condition with high mortality rates and no dedicated treatments.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which fluid builds up in the alveoli, the tiny air sacs in the lungs that exchange oxygen and carbon dioxide. When these sacs fill with fluid, the lungs are unable to take in enough air, resulting in dangerously low oxygen levels in the blood. ARDS most often occurs in people with serious respiratory illnesses such as pneumonia, COVID-19, or sepsis. Despite advances in intensive care, we still know little about how the condition resolves, and mortality rates remain as high as 30 to 50%.

A new study by researchers at the Institute of Science Tokyo (Science Tokyo), Japan, may offer new hope for ARDS treatments. They found that basophils, a rare type of white blood cell, helped resolve lung inflammation in a mouse model of ARDS.

The study, led by Associate Professor Kensuke Miyake and Professor Yasunari Miyazaki, together with Assistant Professor Seiko Takasawa and Specially Appointed Professor Hajime Karasuyama, was published online in the European Respiratory Journal on July 31, 2025.

The findings are in line with previous associations between low basophil counts and severe respiratory failure in conditions such as sepsis and COVID-19. “Using an ARDS mouse model and single-cell RNA sequencing analysis, we found that basophils, previously regarded as ‘bad actors,’ act as ‘good actors’ that suppress lung inflammation,” says Miyake.

Basophils make up only 0.5 to 1% of circulating white blood cells and are best known for their role in allergic reactions. Previous studies, however, have shown that they can also help resolve skin inflammation and bacterial infections. This led the researchers to investigate whether basophils might support recovery from ARDS as well.

In their study, the researchers induced ARDS in mice by introducing bacterial molecules called lipopolysaccharides into the lungs. They then compared mice lacking basophils with mice having normal levels. While both groups showed similar symptoms during the early inflammatory phase, basophil-depleted mice fared worse during recovery, with more lung tissue damage, greater inflammation, and higher numbers of neutrophils—the most common white blood cells and the first responders to infection.

Single-cell RNA sequencing revealed that basophils were a major source of interleukin-4 (IL-4), a signaling molecule that helps immune cells coordinate their responses. When IL-4 was deleted entirely, or when basophils were genetically modified so that they could not produce IL-4, mice showed more lung damage and fluid buildup during recovery.

Further analysis showed that IL-4 acts on neutrophils to switch off genes that drive inflammation, such as Il1a, Il1b, and Cxcl2, and genes that prevent cell death, such as Bcl2a1a, Bcl2a1b, and Bcl2a1d. Without IL-4, neutrophils live longer, remain highly inflammatory, and delay lung recovery.

“We found that during the resolution phase of ARDS, lung-infiltrating basophils produce IL-4, which acts on neutrophils to suppress anti-apoptotic gene expression and the production of pro-inflammatory mediators, thereby alleviating lung inflammation,” says Miyake.

This finding could lead to new treatments that target the basophil–IL-4–neutrophil pathway to improve recovery from ARDS. However, the researchers note that the source of IL-4 in human ARDS remains unknown, making this an important question for future studies.

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About Institute of Science Tokyo (Science Tokyo)
Institute of Science Tokyo (Science Tokyo) was established on October 1, 2024, following the merger between Tokyo Medical and Dental University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the mission of “Advancing science and human wellbeing to create value for and with society.”