Downregulation of CX3CR1 ameliorates experimental colitis: evidence for CX3CL1-CX3CR1-mediated immune cell recruitment

Inflammatory conditions like inflammatory bowel diseases (IBD) are characterized by increased immune cell infiltration. The chemokine ligand CX(3)CL1 and its receptor CX(3)CR1 have been shown to be involved in leukocyte adhesion, transendothelial recruitment, and chemotaxis. Therefore, the objective of this study was to describe CX3CL1-CX3CR1-mediated signaling in the induction of immune cell recruitment during experimental murine colitis. Acute colitis was induced by dextran sodium sulfate (DSS), and sepsis was induced by injection of lipopolysaccharide (LPS). Serum concentrations of CX(3)CR1 and CX(3)CL1 were measured by ELISA. Wild-type and CX(3)CR1(-/-) mice were challenged with DSS, and on day 6, intravital microscopy was performed to monitor colonic leukocyte and platelet recruitment. Intestinal inflammation was assessed by disease activity, histopathology, and neutrophil infiltration. CX(3)CR1 was upregulated in DSS colitis and LPS-induced sepsis. CX(3)CR1(-/-) mice were protected from disease severity and intestinal injury in DSS colitis, and CX(3)CR1 deficiency resulted in reduced rolling of leukocytes and platelets. In the present study, we provide evidence for a crucial role of CX(3)CL1-CX(3)CR1 in experimental colitis, in particular for intestinal leukocyte recruitment during murine colitis. Our findings suggest that CX(3)CR1 blockade represents a potential therapeutic strategy for treatment of IBD.