Selective dependence of kidney dendritic cells on CX3CR1—implications for glomerulonephritis therapy

Abstract

As central regulators of the adaptive immune response, dendritic cells (DCs) are found in virtually all lymphatic and non-lymphatic organs. A compact network of DCs also spans the kidneys. DCs play a central role in maintenance of organ homeostasis as well as in induction of immune responses against invading pathogens. They can mediate protective or destructive functions in a context-dependent manner. We recently identified CX3CR1 as a kidney-specific “homing receptor” for DCs. There was a strong reduction of DCs in the kidneys of CX3CR1-deficient mice compared to controls. This reduction was not observed in other organs except the small intestine. As a possible underlying reason we found a strong expression of the CX3CR1 ligand fractalkine in the kidneys. Due to this CX3CR1-dependent reduction of DCs, especially in the renal cortex, a glomerulonephritis (GN) model was ameliorated in CX3CR1-deficient mice. In contrast, the immune defense against the most common renal infection, bacterial pyelonephritis (PN), was not significantly influenced by CX3CR1-deficiency. This was explained by the much smaller CX3CR1-dependency of medullary DCs, which recruit effector cells into the kidney during PN. Additionally, once neutrophils had been recruited by mechanisms distinct from CX3CR1, they carried out some of the functions of DCs. Taken together, we suggest CX3CR1 as a therapeutic target for GN treatment, as the absence of CX3CR1 selectively influences DCs in the kidney without rendering mice more susceptible towards bacterial kidney infections.