New research suggests that lung fibrosis develops when scar tissue cells escape immune surveillance, suggesting potential therapy.
Idiopathic lung fibrosis is a debilitating disease with a dismal prognosis. It’s caused by progressive scarring in the lungs, making it difficult to breathe, and patients become dependent on oxygen. Treating the disease is a challenge because it’s unclear why the scarring begins and spreads.
Now a team of researchers led by assistant professor of pathology Gerlinde Wernig, MD, at the Stanford Institute for Stem Cell Biology and Regenerative Medicine, has shown that scar tissue cells called fibroblasts are able to proliferate by avoiding immune surveillance, much like cancer cells. A therapy may lie in reactivating that immune function.
The work was published online in Nature Communications in June.
Immune surveillance is the process the body uses to keep tissues healthy and to eliminate cells that might cause disease. For instance, roving immune cells detect and remove pre-cancerous cells. More advanced cancer cells can resist this process by presenting protective molecular signals.
One of these protective signaling proteins, CD47, is used by cancer cells as a “don’t eat me” signal that stops immune cells called macrophages from devouring cells. Another, called PD-L1, is sometimes used by aberrant cells to keep macrophages and other immune cells called T-cells from attacking them.
“In idiopathic lung disease, these fibroblasts behave almost like cancer cells,” Wernig said. “They grow over normal lung structures, obliterating airways and blocking the passage of air in and out of the blood.” Like cancer cells, Wernig has discovered, fibroblasts also evade the immune system using these immune-dampening proteins.
In previous work, Wernig and her colleagues showed that a gene called JUN is a master regulator of fibrotic processes in mice. Expression of the gene caused fibrosis of the lung, liver, skin, bone marrow and the kidney in mice. In the current work, Wernig and her colleagues showed that in tissue samples from end-stage lung fibrosis patients, JUN directly activates the genes for CD47 and PD-L1, leading to increased production of these proteins in fibrotic scar-forming lung cells.