Dr. Alex Barron an immunologist and stromal cell biologist with 18 years of experience. Currently he leads an immunology team at Pfizer discovering new targets and developing drugs for patients with cancers and inflammatory diseases.

A Broadly Fibrogenic Macrophage Subset Induced by Type 3 Inflammation

Identifying the fibrogenic macrophages in human fibrotic tissues could lead to new and more effective treatments for fibrosis. We used complementary techniques to identify a subset of CD9+ TREM2+ macrophages expressing SPP1, GPNMB, FABP5, and CD63 in human and murine liver and lung fibrosis. These macrophages expanded at the edges of scars adjacent to activated fibroblasts. Neutrophils producing the type 3 cytokines GM-CSF and IL-17A clustered with these scar-associated macrophages. Using primary human cells in vitro, we determined that GM-CSF, IL-17A and TGF-β1 drive the differentiation of these scar-associated macrophages. Co-culture of monocyte-derived macrophages with fibroblasts and TGF-β1 augmented type 1 collagen deposition. In vivo inhibition of GM-CSF, IL-17A or TGF-β1 reduced scar-associated macrophage expansion and hepatic and pulmonary fibrosis. Our work links a specific scar-associated macrophage population with fibrosis across species and tissues.

3:50pm Snacks & Socializing
4:10pm Talk Begins