A research team at the University of Arizona has recently made a breakthrough in the mechanism of scar formation. They discovered a previously unknown population of immune cells circulating in the blood that plays a central role in driving systemic fibrosis—the excessive proliferation of abnormal scar tissue. This research, published in *Nature Biomedical Engineering*, not only refreshes the scientific community's understanding of the wound healing process but also provides new potential therapeutic directions for preventing and even reversing fibrosis.

Fibrosis is one of the leading causes of death in nearly half of all deaths in developed countries. It affects multiple organs, including the lungs, liver, kidneys, and heart, and can lead to serious conditions such as organ transplant rejection and non-alcoholic steatohepatitis. However, there are currently no FDA-approved treatments worldwide that can directly treat or prevent fibrosis.

“When any tissue is injured, the body initiates a complex healing process to form scars. The fibrosis that occurs during this process can eventually lead to organ failure and has become one of the leading causes of death in the United States,” explained Karen Chen, associate professor of surgery at the University of Arizona, Tucson School of Medicine and co-first author of the study. “In our study, we identified a special type of immune cell circulating in the blood that is one of the key drivers of fibrosis in multiple organs throughout the body.”

The research team discovered in animal models and in vitro human cell experiments that interfering with the signals emitted by these immune cells during the healing process can significantly reduce scar tissue formation. Simultaneously, the activity of these cells was also significantly upregulated in human fibrotic skin and liver tissue samples.

Wound healing typically involves several precisely coordinated stages, including hemostasis, inflammation clearance, and the growth and remodeling of new tissue. When the early inflammatory response is abnormally persistent or repair is dysregulated, pathological scarring occurs. Previous research has focused primarily on the role of immune cells in the early inflammatory stages, while their role in later repair is poorly understood.

The study's lead author, Dr. Jeffrey Gertner, Chair of the Department of Surgery at Tucson Medical School, and Professor Chen further revealed that myeloid cells, including immune and inflammatory cells, actively promote scar formation by activating a series of cell signaling pathways, while simultaneously inhibiting the activity of cells with anti-inflammatory effects. Once this signaling pathway is blocked, the cells' "behavioral pattern" undergoes a fundamental shift: from building scars to supporting normal tissue regeneration, and the function of anti-inflammatory cells is restored.

In the experiment, researchers observed that the healed tissue after signal intervention was thinner, with collagen arrangement more closely resembling normal skin, and significantly reduced signs of fibrosis. This suggests a dynamic interaction between mechanical force signals and immune regulation during the healing process, which may represent a novel therapeutic target for combating fibrosis in the skin and even internal organs.

“This work fundamentally changes our understanding of fibrosis,” Dr. Gertner emphasized. “By targeting immune cells that can sense mechanical forces, circulate throughout the body, and drive abnormal repair, we may be able to prevent or even reverse fibrosis in multiple organs, from the skin and lungs to the heart and liver, in the future.”

The research team also includes Dr. William Hahn, Dr. Mohammad Khreiss, Dr. Maria Gracia Mora Pinos, and many other scientists and students. Currently, the findings have laid an important scientific foundation for the development of next-generation anti-fibrotic therapies.