Parabiosis reveals leukocyte dynamics in the kidney

The immune cellular compartment of the kidney is involved in organ development and homeostasis, as well as in many pathological conditions. Little is known about the mechanisms that drive intrarenal immune responses in the presence of renal tubular and interstitial cell death. However, it is known that tissue-resident leukocytes have the potential to have distinct roles compared with circulating cells. We used a parabiosis model in C57BL/6 CD45 congenic and green fluorescent protein transgenic mice to better understand the dynamics of immune cells in the kidney. We found F4/80Hi intrarenal macrophages exhibit minimal exchange with the peripheral circulation in two models of parabiosis, whether mice were attached for 4 or 16 weeks. Other intrarenal inflammatory cells demonstrate near total exchange with the circulating immune cell pool in healthy kidneys, indicating that innate and adaptive immune cells extensively traffic through the kidney interstitium during normal physiology. Neutrophils, dendritic cells, F4/80Low macrophages, T cells, B cells, and NK cells are renewed from the circulating immune cell pool. However, a fraction of double-negative T (CD4- CD8-) and NKT cells are long-lived or tissue resident. This study provides direct evidence of leukocyte sub-populations that are resident in the renal tissue, cells which demonstrate minimal to no exchange with the peripheral blood. In addition, the data demonstrate continual exchange of other sub-populations through uninflamed tissue.