Identifying novel biologically relevant interactions between lymph node stroma and innate immune cells

Fibroblastic reticular cells (FRCs) are found in secondary lymphoid organs where they strongly shape adaptive immunity. However, interactions with immunologically important macrophage and neutrophil populations are completely undescribed. I recently found evidence that FRCs directly induce monocyte differentiation, and they attract macrophages and then arrest their migration. I also found that FRCs express a gene signature highly relevant to macrophage and neutrophil influx and function and that expression of key chemokines increases immediately after LPS exposure. As robust proof-of-principle, FRC depletion reduces macrophage numbers by 95% in lymph nodes. I hypothesise that FRCs fundamentally regulate macrophages and neutrophils in secondary lymphoid organs.

I will test FRC interactions with macrophages and neutrophils through co-culture and live cell imaging, developing relevant data, inhibit key factors produced by stroma, examining effects on macrophage and neutrophil migration, phenotype and function. I will also use a targeted in vivo model of FRC depletion (FAP-DTR) to dissect FRC-mediated control of macrophages and neutrophil function.