Systemic lupus erythematosus (lupus) is a multi-organ autoimmune disease with 5-10% mortality in 10 years. Both skin and kidney (lupus nephritis, LN) are severely affected and sensitivity to ultraviolet (UV) sunlight rays affecting ~ 80% of patients can lead to LN flares. The cellular and molecular mechanisms linking skin inflammation caused by UV light and kidney injury are unknown.
The overall objectives of this projects are to:
- Demonstrate mechanisms by which neutrophils migrating from UV-exposed skin damage glomerular and tubular cells to trigger LN flares
- Elucidate the role of a novel CD177high neutrophil population in kidney injury
- Define the role of UV-induced type I interferon (IFN-I) response on neutrophil interactions with and damage of kidney structural cells, on a single-cell basis
The central hypothesis is that neutrophils recruited to the kidney following skin UV exposure mediate acute podocyte and distal tubular loss and injury, and lead to chronic mesangial fibrosis potentiated by type I interferon. The rationale for this project stems from the gap in the knowledge of how neutrophils mediate kidney injury in lupus.