Exclusive CX^sub 3^CR1 dependence of kidney DCs impacts glomerulonephritis progression

DCs and macrophages both express the chemokine receptor CX3CR1. Here, the authors have demonstrated that its ligand, CX^sub 3^CL1, is highly expressed in the murine kidney and intestine. CX^sub 3^CL1 deficiency markedly reduced DC numbers in the healthy and inflamed kidney cortex, and to a lesser degree in the kidney medulla and intestine, but not in other organs. CX^sub 3^CL1 also promoted influx of DC precursors in crescentic glomerulonephritis, a DC-dependent aggressive type of nephritis. Primarily CX^sub 3^CL1-dependent DCs in the kidney cortex processed antigen for the intrarenal stimulation of T helper cells, a function important for glomerulonephritis progression. In contrast, medullary DCs played a specialized role in inducing innate immunity against bacterial pyelonephritis by recruiting neutrophils through rapid chemokine production. These findings demonstrate that, cortical and medullary DCs play specialized roles in their respective kidney compartments. They identify CX^sub 3^CL1 as a potential therapeutic target in glomerulonephritis that may involve fewer adverse side effects, such as impaired anti-infectious defense or compromised DC functions in other organs.