Disease relevance of Cx3cr1

• Decreased atherosclerosis in CX3CR1-/- mice reveals a role for fractalkine in atherogenesis [1].
• CX3CR1 is the first chemokine receptor shown to contribute to fibrogenesis in renal ischemia-reperfusion injury [2].
• Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia-reperfusion injury [2].
• In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1-/- mice showed more extensive neuronal cell loss than Cx3cr1+ littermate controls [3].
• The results also point to the potential therapeutic usefulness of CX3CL1 inhibition and/or blockade of CX3CL1-CX3CR1 interaction in idiopathic inflammatory myopathy [4].

High impact information on Cx3cr1

• Thus, G glycoprotein interaction with CX3CR1 probably plays a key role in the biology of RSV infection [5].
• Following peripheral lipopolysaccharide injections, Cx3cr1-/- mice showed cell-autonomous microglial neurotoxicity [3].
• Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1) [3].
• Both types of precursors displayed similar phenotypes and gave rise to CX3CR1/green fluorescent protein (GFP)-positive Mphi, but differed by their differentiation potential, at the clonal level [6].
• Because interleukin-15 (IL-15) is an essential cytokine for NK cell development and maintenance, we hypothesized that it may induce CX3CR1 expression on this cell type [7].

Biological context of Cx3cr1

• Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion [8].
• RESULTS: Fkn analogs truncated by >/=4 amino acid residues from the N-terminus failed to induce chemotaxis and calcium influx by CX3CR1-expressing cells [9].
• Here we demonstrate by both gene inactivation and target protein blockade that a single chemokine receptor subtype, the fractalkine receptor CX3CR1, is able to reduce both inflammation and fibrosis after ischemia-reperfusion injury in the mouse, leading to partially preserved renal function after injury [2].
• Our results suggest that CX3CL1-CX3CR1 interaction plays an important role in inflammatory cell migration into the muscle tissue of EAM mice [4].
• Consistent with previous reports, our data indicate that the activity of CX3CR1 on resting monocytes is sufficient to mediate cell adhesion to CX3CL1 [10].

Anatomical context of Cx3cr1

• The Chemokine Receptor CX3CR1 Mediates Homing of MHC class II-Positive Cells to the Normal Mouse Corneal Epithelium [11].
• CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance [12].
• Lamina propria DCs were found to depend on the chemokine receptor CX3CR1 to form transepithelial dendrites, which enable the cells to directly sample luminal antigens [12].
• In the affected muscles of EAM mice, CX3CL1 (fractalkine) was expressed on the infiltrated mononuclear cells and endothelial cells, and its corresponding receptor, CX3CR1, was expressed on the infiltrated CD4 and CD8 T cells and macrophages [4].
• Resident microglia associated with the parenchyma and macrophages in the meninges and choroid plexus constituitively express CX3CR1 [13].

Associations of Cx3cr1 with chemical compounds

• Acute inflammatory responses in the CNS, induced by stereotaxic injections of lipopolysaccharide or kainic acid, results in activation of microglia and astrocytes but no detectable changes in the glial expression of CX3CL1 or CX3CR1 [13].
• METHODS AND RESULTS: Here, we show that oxidized linoleic acid metabolites, which are components of oxidized LDL found in large amounts in atherosclerotic plaque, were able to specifically induce differentiation of human monocytes to macrophages with decreased expression of CCR2, confirming a previous report, and increased expression of CX3CR1 [14].

Regulatory relationships of Cx3cr1

• Treatment with RANTES specifically modulated astrocyte receptors upregulating intercellular adhesion molecule 1 (ICAM-1) and downregulating CX3CR1 expression [15].

Other interactions of Cx3cr1

• In a prion model of chronic neurodegeneration and inflammation, CX3CL1 immunoreactivity is upregulated in astrocytes and CX3CR1 expression is elevated on microglia [13].

Analytical, diagnostic and therapeutic context of Cx3cr1

• A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection [16].
• Immunohistochemistry was performed using primary antibodies recognizing soluble and membrane-bound CX3CL1 and the N-terminus of the CX3CR1 [13].
• METHODS AND RESULTS: Femoral arteries of CX3CR1-/- and wild-type (WT) mice were injured with an angioplasty guide wire [17].

References