Anna Ruta, PhD
Johns Hopkins School of Medicine
Gamma Delta (GD) T Cells Interact with Stromal Cells to Modulate Matrix Composition and Vascularity in Foreign Body Response to Synthetic Implants
Immune-stromal crosstalk governs tissue fibrosis, which is marked by dysregulated extracellular matrix (ECM) production and aberrant vasculature. Here, we investigate how gamma delta (gd) T cells interact with stromal cells to shape fibrosis in the foreign body response. During the acute reaction, type-1 (gdIFNg) and type-17 (gd17) effector subsets accumulated at the implant site. While gdIFNg cells decreased as fibrosis progressed, activated gd17 cells persisted as dominant interleukin-17 producers. The gd17 cells increased with aging and high-fat diet, both factors associated with chronic inflammation and fibrosis. Fibroblasts co-cultured with gd17 cells exhibited increased expression of collagen genes and intercellular communication inference linked gd T cell ligands to activation of ECM remodeling and vascular development programs in fibroblasts and endothelial cells, respectively. Finally, deletion of gd T cells using a TCRd-/- murine strain altered expression of ECM components and increased vessel size within the fibrotic matrix. Altogether, our findings implicate gd T cells in regulating stromal behavior to modulate composition and vascularity of fibrotic tissues.
Immune-stromal crosstalk governs tissue fibrosis, which is marked by dysregulated extracellular matrix (ECM) production and aberrant vasculature. Here, we investigate how gamma delta (gd) T cells interact with stromal cells to shape fibrosis in the foreign body response. During the acute reaction, type-1 (gdIFNg) and type-17 (gd17) effector subsets accumulated at the implant site. While gdIFNg cells decreased as fibrosis progressed, activated gd17 cells persisted as dominant interleukin-17 producers. The gd17 cells increased with aging and high-fat diet, both factors associated with chronic inflammation and fibrosis. Fibroblasts co-cultured with gd17 cells exhibited increased expression of collagen genes and intercellular communication inference linked gd T cell ligands to activation of ECM remodeling and vascular development programs in fibroblasts and endothelial cells, respectively. Finally, deletion of gd T cells using a TCRd-/- murine strain altered expression of ECM components and increased vessel size within the fibrotic matrix. Altogether, our findings implicate gd T cells in regulating stromal behavior to modulate composition and vascularity of fibrotic tissues.
