Supporting players could be the key to autoimmune treatment

In April 2022, scientists in the lab of Prof. Ido Amit, from the Department of Systems Immunology, demonstrated that a subset of supporting cells called fibroblasts may lie at the origins of a devastating, incurable autoimmune disorder called scleroderma, pointing the way toward possible future treatments.

Scleroderma, which afflicts mainly women aged 30-50, is characterized by the formation of an abnormally hard, inflexible layer of skin on the arms, legs and face. In about a third of the cases, the disease spreads beyond the extremities, causing life-threatening damage to internal organs. Existing immune-regulating drugs are inadequate in scleroderma.

Dr. Chamutal Gur, a rheumatologist at Hadassah University Medical Center in Jerusalem and a postdoctoral fellow in the Amit lab, led the new study. She and her colleagues used single-cell RNA sequencing technologies developed in the Amit lab to reveal each cell’s unique identity. The study was conducted in collaboration with colleagues at Hadassah and at the Rambam Health Care Campus in Haifa.

The researchers found that rather than a global pattern of immune abnormalities in scleroderma patients, their fibroblasts were what differed significantly from those of the controls. The study also found that fibroblasts, previously dismissed as mere “scaffolding,” can be divided into about 10 major groups, each performing different and often vital functions.

Most importantly, the scientists identified a subset of fibroblast whose concentration drops sharply in the early stages of scleroderma. They named these cells scleroderma-associated fibroblasts (ScAFs).

The researchers mapped the locations of ScAFs deep within skin tissue and tapped these cells’ RNA to determine what changes a functional ScAF into a malfunctioning cell common in scleroderma patients. They also identified biological markers correlated with specific kinds of organ damage; these markers can help physicians administer personalized treatments, preventing life-threatening complications. The research also revealed ScAF-related signaling pathways that can be targeted in future scleroderma therapies.

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

Prof. Ido Amit’s research is supported by the Adelis Foundation; Miel de Botton; the Elsie and Marvin Dekelboum Family Foundation; the Dwek Institute for Cancer Therapy Research; the Hadar Impact Fund; the Morris Kahn Institute for Human Immunology; the Moross Integrated Cancer Center; the Schwartz Reisman Collaborative Science Program; the Swiss Society Institute for Cancer Prevention Research; the Thompson Family Foundation Alzheimer’s Disease Research Fund; the Vainboim Family. The Garvan-Weizmann Partnership Scheinberg Fellowship supports a postdoctoral fellow in the Amit lab. Prof. Amit is the incumbent of the Eden and Steven Romick Professorial Chair.