A comprehensive immune cell atlas of cystic kidney disease reveals the involvement of adaptive immune cells in injury mediated cyst progression

It is widely accepted that injuries to cilia mutant mice accelerate the rate of cystic kidney disease; however, cellular factors that drive the accelerated rate of cystic disease are unknown. By performing single cell RNA sequencing of all CD45+ immune cells, we find that the subtype and gene expression of adaptive immune cells is significantly altered between non-injured, aged cystic mice, injury-accelerated cystic mice, and non-cystic controls. Deletion of all adaptive immune cells reduced cystic disease in the injury-accelerated model but had no effect on cystic disease in the non-injured model. This differential rescue may be due to unique adaptive immune cell subtypes and ligands that are only present in the injury accelerated model of cystic disease. To unbiasedly identify modifier cells that may be influencing the differential rate of cyst growth observed in injured versus non-injured cilia mutant kidneys at a time of similar cyst severity, we generated a single cell atlas of cystic kidney disease by sequencing 79,355 cells from control mice and adult induced conditional Ift88 mice (hereafter referred to as cilia mutant mice) that were harvested ~7 months post induction or 8 weeks post 30-minute unilateral ischemia reperfusion injury.