Topic Overview:

Tissue fibrosis is a leading cause of morbidity and mortality for a number of human diseases. Despite its important impact on human health, inadequate understanding of the mechanisms underlying the initiation and progression of fibrosis limits the development of effective therapeutics for fibroproliferative diseases. Fuschiotti’s research focuses on systemic sclerosis (SSc), a connective tissue disease characterized by vascular damage, inflammation, and cutaneous and visceral fibrosis.

T cells are the predominant inflammatory infiltrate in the affected tissues and are thought to produce cytokines that drive the synthesis of extracellular matrix proteins in fibroblasts, resulting in excessive fibrosis. Fuschiotti and colleagues have shown that peripheral blood effector CD8+ T cells from SSc patients produce high levels of the profibrotic cytokine IL-13 compared to other inflammatory conditions and healthy controls. This abnormality is critical for predisposing patients to more severe forms of cutaneous disease, and Fuschiotti and colleagues have found that it is associated with defects in the molecular control of IL-13 production. Fuschiotti will present recent data showing that IL-13 and CD8+ T cells are already present in high levels in the early skin lesions of SSc, which further supports their roles in driving the pathogenesis of SSc. Further, she will develop a hypothesis that CD8+ T cells are involved in the onset of cutaneous systemic sclerosis by aberrant production of profibrotic IL-13 and cytotoxic damage.

This ongoing work aims to describe the unique role of CD8+ T cells in the pathogenesis of SSc and to elucidate the cellular and molecular mechanisms leading to tissue damage and fibrosis in SSc. New insights into disease pathogenesis will offer novel therapeutic targets that may be exploited for the treatment of SSc, where none currently exist, as well as for other fibrosing disorders.