The Korea National Institute of Health (KNIH) has identified an immune mechanism that exacerbates the progression of idiopathic pulmonary fibrosis, an intractable disease in which the lungs harden. The finding is evaluated as a potential new target for developing treatment strategies for pulmonary fibrosis.
The KNIH under the Korea Disease Control and Prevention Agency announced Friday that it has published research confirming the role of the ATF3 gene, which regulates abnormal immune responses during pulmonary fibrosis progression, in the international journal Clinical Science.
Idiopathic pulmonary fibrosis is an intractable disease in which lung tissue gradually hardens for unknown reasons, causing respiratory function to decline. Treatments such as pirfenidone and nintedanib are currently in use, but they only slow the progression of the disease, creating a need to identify new therapeutic targets.
The researchers induced pulmonary fibrosis in experimental animals with ATF3 deficiency and analyzed changes in immune responses and lung function. The results showed that when ATF3 was absent, pulmonary fibrosis progressed more severely than in the normal group, and lung function decline was also pronounced. Lung capacity decreased by about 20 to 25 percent, and while lung elasticity increased, lung compliance decreased, confirming that the lungs became stiffer.
Changes in immune cells were also distinct. In the ATF3-deficient group, neutrophils responsible for the initial inflammatory response increased more than tenfold, and M2c macrophages that promote fibrosis also increased 6.5-fold. Transcriptome analysis showed that expression of genes related to inflammation and fibrosis increased more than 1.5-fold.
This demonstrates that ATF3 is a key regulatory factor that suppresses excessive immune responses and alleviates the progression of pulmonary fibrosis. The researchers see potential for regulating the ATF3 pathway to be utilized as a future treatment strategy for pulmonary fibrosis.
"Since pulmonary fibrosis is a chronic lung disease that is difficult to treat, new treatment strategies are important," said Kim Won-ho, director of the Division of Chronic Disease Convergence Research at the KNIH. "We will continue research that identifies the mechanisms of chronic respiratory diseases and can lead to actual patient treatment."
