Macrophage and Fibroblast Crosstalk in the RA Synovium

Hospital For Special Surgery, New York NY

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Macrophages represent key cellular drivers of chronic joint inflammation in rheumatoid arthritis (RA). Recently, synovial fibroblasts have also emerged as active players in this disease. Interestingly, fibroblasts and other mesenchymal stromal cells impart immunosuppressive activity in a wide-range of tissues. Here we wish to explore how rampant inflammation persists in RA despite a massive outgrowth of fibroblasts. Our preliminary evidence suggests that RA synovial fibroblasts indeed promote anti-inflammatory pathways in macrophages. In the context of the RA inflammatory milieu, we propose this results in a mixed pro-inflammatory and wound- healing macrophage phenotype. As wound-healing macrophages support fibroblast function, we are interested in whether induction of wound-healing responses in RA macrophages ultimately feeds back to support fibroblast expansion and invasiveness. This ultimately may establish a perpetual crosstalk cycle, which promotes survival of both cell types, inflammation and tissue damage. RA afflicts over 1 million Americans. Current therapies target pro-inflammatory macrophage responses. Here we propose that macrophage wound healing responses may also represent critical therapeutic targets, as these responses may promote fibroblast-mediated RA pathogenesis. The candidate obtained a PhD in immunology from Columbia University and pursued postdoctoral fellowship at Rockefeller University in epigenetics and cell signaling. She is now motivated to apply her rigorous basic science training towards establishing an academic career in clinically relevant research focused on the pathophysiology of RA. In order to meet this goal, she will conduct research in the laboratory of Lionel Ivashkiv at Hospital for Special Surgery, where she will gain significant experience working with human tissue and a deeper understanding of rheumatic diseases from the clinical perspective. Dr. Ivashkiv is a board certified rheumatologist, an expert in cytokine-mediated inflammatory responses and has trained scientists who now hold faculty positions.