Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034186 (pyelonephritis)
 6,144 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DCs and macrophages both express the chemokine receptor CX3CR1. Here we demonstrate that its ligand, CX3CL1, is highly expressed in the murine kidney and intestine. CX3CR1 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. CX3CR1 also promoted influx of DC precursors in crescentic glomerulonephritis, a DC-dependent aggressive type of nephritis. Disease severity was strongly attenuated in CX3CR1-deficient mice. Primarily CX3CR1-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. CX3CR1 deficiency had little effect on the immune defense against pyelonephritis, as medullary DCs were less CX3CR1 dependent than cortical DCs and because recruited neutrophils produced chemokines to compensate for the DC paucity. These findings demonstrate that cortical and medullary DCs play specialized roles in their respective kidney compartments. We identify CX3CR1 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.
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PMID:Exclusive CX3CR1 dependence of kidney DCs impacts glomerulonephritis progression. 2399 31

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 CX(3)CR1 as a kidney-specific "homing receptor" for DCs. There was a strong reduction of DCs in the kidneys of CX(3)CR1-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 CX(3)CR1 ligand fractalkine in the kidneys. Due to this CX(3)CR1-dependent reduction of DCs, especially in the renal cortex, a glomerulonephritis (GN) model was ameliorated in CX(3)CR1-deficient mice. In contrast, the immune defense against the most common renal infection, bacterial pyelonephritis (PN), was not significantly influenced by CX(3)CR1-deficiency. This was explained by the much smaller CX(3)CR1-dependency of medullary DCs, which recruit effector cells into the kidney during PN. Additionally, once neutrophils had been recruited by mechanisms distinct from CX(3)CR1, they carried out some of the functions of DCs.Taken together, we suggest CX(3)CR1 as a therapeutic target for GN treatment, as the absence of CX(3)CR1 selectively influences DCs in the kidney without rendering mice more susceptible towards bacterial kidney infections.
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PMID:Selective Dependence of Kidney Dendritic Cells on CX3CR1--Implications for Glomerulonephritis Therapy. 2632 46