Giuseppina Farina, M.D., Ph.D. – Norma Nadeau/Mary Van Neste New England Chapter Research Grant
Boston Univ. School of Medicine, Boston, Ma.

"Interferon Signature in Scleroderma Skin and TLR on Fibroblasts"

Established Investigator

Fibrosis is responsible for the majority of clinical problems in patients with diffuse cutaneous systemic sclerosis, including skin, lung, kidney, and gastrointestinal disorders. Little is know about how inflammation in SSc might lead to scarring/fibrosis. Recent studies have shown how inflammation can be activated in white
blood cells by receptors on their surface referred to as toll-like receptors (TLRs). The goal of this proposal is to better understand how TLRs might stimulate fibrosis in SSc. In particular, we will study the relationship between two key proteins that act to communicate between cells: interferon (IFN), a key signal of inflammation, and transforming growth factor-beta, a key signal for scarring/fibrosis. There are currently several reasons to think that both of these key signals are made by white blood cells upon TLR activation. They may work together or against each other to control scarring/fibrosis. We will study how TLRs regulate these proteins both in skin from SSc patients, in cells cultured in incubators from SSc patients, and in mouse skin. These studies are likely to provide important information about the cause of scarring/fibrosis in SSc and also to planning of clinical trials using medicines designed to block IFN in patients with SSc.