Researchers Discover Natural Mechanism That Resolves Lung Fibrosis in Mice

Researchers Discover Natural Mechanism That Resolves Lung Fibrosis in Mice

Scientists found that a special kind of white blood cell could potentially be stimulated to migrate to the lungs of idiopathic pulmonary fibrosis (IPF) patients and help repair fibrosis damage. They showed how this process occurs naturally in mice with lung fibrosis.

The study, “TRAIL-Dependent Resolution of Pulmonary Fibrosis,” was published in the journal Mediators of Inflammation.

IPF involves scarring, or fibrosis, in the lungs, which leads to a decrease in their function. Activated fibroblasts and myofibroblasts are cells involved in scarring, and are thought to be responsible for the injury seen in IPF.

Studies have shown that white blood cells — myeloid cells — that carry a protein called tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on their surfaces help to resolve fibrosis. These cells originate in the bone marrow and are induced to travel to the site of fibrosis in the body, where they block the activity of offending fibroblasts and myofibroblasts.

In the study, TRAIL-positive myeloid cells were used to block the activation of myofibroblasts in mice with lung fibrosis.

Given the fact that mice with lung fibrosis can improve on their own, the researchers were able to stop such improvement by eliminating TRAIL-positive myeloid cells, showing that these cells indeed play a key role in counteracting fibrosis development.

The same cells were found to be present in lower numbers in lung tissue from IPF patients when compared to healthy people.

However, the team believes that the presence of TRAIL+ myeloid cells in the lungs is not enough to produce the beneficial effect seen in fibrosis, and hypothesized that there must also be receptors on fibroblasts and myofibroblasts that bind the TRAIL protein on myeloid cells to block them.

These receptors would also be decreased in the lungs of IPF patients, which would logically make the fibroblasts and myofibroblasts less sensitive to the activity of TRAIL+ myeloid cells.

While the beneficial effect of inducing TRAIL-positive myeloid cells to migrate from the bone marrow to the lungs is a promising approach to therapy, the researchers emphasized that methods to sensitize fibroblasts and myofibroblasts to the effect of TRAIL-positive white blood cells must be identified first.

“Based on the present studies, TRAIL remains an attractive therapeutic target in IPF after strategies are identified that sensitize myofibroblasts to TRAIL-induced inhibitory effects,” they wrote.

“Together, these results identified TRAIL+ myeloid cells as a critical mechanism in the resolution of pulmonary fibrosis, and strategies directed at promoting its function might have therapeutic potential in IPF,” the team concluded.

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