Type of immune cell may be key driver of scleroderma scarring: Study

Targeting macrophages could be effective in disease prevention written by Marisa Wexler, MS | February 3, 2026

Macrophages, a type of immune cell, may be mainly responsible for driving fibrosis, or scarring, in people with scleroderma, according to new research done in animal models.

“These data suggest that a single cell type, macrophage, may be responsible for inducing scleroderma,” Sanja Arandjelovic, PhD, who co-led the study at the University of Virginia, said in a university news story. “Although more research is needed on understanding whether targeting these cells later during disease progression can reverse the existing tissue damage, our data suggest that macrophage inhibition could be effective in disease prevention in the high-risk patient population.”
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The study, “Macrophages Are Critical Inducers of Bleomycin-Induced Fibrosis in a Systemic Scleroderma Model,” was published in The American Journal of Pathology.

Reducing macrophage activation effectively prevented fibrosis
Scleroderma is an inflammatory disease marked by excessive fibrosis that can affect the lungs and other organs, interfering with organ function. The exact biological mechanisms driving fibrosis in scleroderma are not fully understood, making it difficult to develop effective therapies for the disease.

Macrophages are immune cells that play key roles in fighting infection and also act as the body’s trash collectors, helping to dispose of debris such as dead cells. Macrophages are also known to help coordinate the formation of scar tissue, which is normally an important part of the body’s natural healing processes. However, the new study shows that abnormal macrophage activation may drive excessive fibrosis in scleroderma.

The researchers first observed that levels of macrophages with profibrotic features were markedly elevated in the skin and lungs of two mouse models of scleroderma, correlating with high collagen content characteristic of fibrotic tissue.

In a mouse model of fibrosis induced by the chemical bleomycin, the researchers found that reducing macrophage activation using two different approaches effectively prevented fibrosis.

Further tests in this mouse model and in human macrophages showed that these immune cells had reduced ability to clear cellular debris, and they secreted more profibrotic signaling molecules. When the researchers injected macrophages from bleomycin-exposed mice into healthy mice, the healthy mice developed widespread fibrosis similar to scleroderma.

This shows that macrophages may drive the disease, at least in this model, lending further support to the idea that targeting these cells may be key to treating scleroderma.

“Collectively, this work identifies macrophages as critical promoters of tissue fibrosis and suggests that inhibition of macrophage activation represents a new potent therapeutic avenue in efforts to reverse fibrosis associated with chronic inflammation,” the researchers concluded.

The researchers noted that there are already medications that target macrophages, so it may be possible to repurpose existing therapies to target these cells.
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“Clinically approved therapies that target macrophages already exist,” Arandjelovic said. “Repurposing these treatments for use in scleroderma would be an exciting next step in finding new therapies for this devastating disease.”