Researchers have found another piece in the molecular puzzle of changes leading to pulmonary fibrosis — a cell signaling factor.
It offers scientists a new target for developing lung-scarring treatments.
Lung damage leads to the production of a protein that attracts immune cells to the area. Without this signaling, mice develop a milder form of pulmonary fibrosis, the study in the journal Scientific Reports showed.
The protein, CX3CL1, binds to a receptor on the surface of immune cells called macrophages. Scientists have studied abnormal CX3CL1 signaling in a lot of diseases, the research team at Wakayama Medical University in Japan noted.
Since macrophages are in the lungs when scarring occurs, the team set out to explore whether the protein could be involved in the scarring.
The study involved mice that were exposed to the fibrosis-triggering chemical bleomycin. The team titled their work “Essential involvement of the CX3CL1-CX3CR1 axis in bleomycin-induced pulmonary fibrosis via regulation of fibrocyte and M2 macrophage migration.”
As the researchers suspected, mice produced more CX3CL1 in their lungs after being exposed to bleomycin. This attracted macrophages to the lungs, but also fibrosis-generating cells called fibroblasts.
The team then looked at how mice that had been genetically engineered to lack the CX3CR1 receptor would respond to bleomycin. Without the signaling, their lung disease became much milder, with a lot less scarring.
The difference in scarring between mice with and without bleomycin did not stem from levels of macrophages in their lungs — because the levels were the same. Instead, researchers found that the macrophages’ behavior was different in the two groups of mice.
Scientists know that the immune cells take on one of two activation states, M1 or M2. They have linked the M2 state to both anti-inflammatory processes and the development of fibrosis diseases.
The Japanese team discovered that lack of CX3CL1 signaling led to the immune cells taking on an M1 state, reducing the severity of scarring.
This was not the only change that lack of CX3CR1 generated. Researchers also discovered that the mice’s lungs contained fewer fibrocytes, or cells involved in fibrosis development.
The genetically altered mice also had lower levels of TGF-beta, a protein that promotes scarring.
Together, the results showed that CX3CL1 is part of the complex molecular process that guards against lung scarring. The findings offer researchers another angle to explore in their quest for more effective treatments for the condition.