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Scleroderma: Role of fibroblasts identified

Frontal linear scleroderma. Photo by Gambichler et al. via Wikimedia Commons

New findings suggest that a subset of fibroblasts may play a key role in the development of scleroderma, a finding researchers suggest could lead to future therapies for this disease.

Published in Cell (April 4, 2022), the research involved collecting skin samples from nearly 100 scleroderma patients and from more than 50 healthy volunteers who served as a control group. The investigators used single-cell RNA sequencing to identify the specific cells in each sample.

Because scleroderma is considered an autoimmune condition, the researchers looked for immune cell differences between the control and patient groups. But contrary to what would be expected of an autoimmune disease, the analysis failed to reveal a characteristic, global pattern of immune abnormalities in most of the patients. Instead, the researchers found the cell differences between the scleroderma patients and the controls were related to the fibroblasts.

Rather than fibroblasts being simply a sort of cellular ‘scaffolding’, the researchers found that fibroblasts can be divided into about ten major groups, each performing different functions. These functions ranged from conveying immune system signals to affecting metabolism, blood clotting and blood vessel formation. In total, the investigators were able to sort fibroblasts into 200 subtypes.

They identified a specific subset of fibroblasts whose concentration drops sharply in the early stages of scleroderma. They named these cells Scleroderma-Associated Fibroblasts, abbreviated as ScAFs. Whereas in healthy controls ScAFs accounted for nearly 30% of all fibroblasts, this percentage decreased dramatically in scleroderma patients and continued to plummet as the disease progressed.

Investigators then mapped out where ScAFs are found in the deep skin, identified genetic changes related to ScAF malfunctions seen in scleroderma patients, and identified potential therapeutic targets related to malfunctioning ScAFs.

“The reduction in the size of a critical subset of fibroblasts appears to be an early event in the course of scleroderma,” said senior author Ido Amit, PhD, in a press release. “It might be possible to design a therapy that will make up for this loss, slowing the progression of the disease.”

Dr. Amit is a Professor of Immunology, at the Weizmann Institute of Science, Rehovot, Israel.


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