title: Downregulation of CX3CR1 ameliorates experimental colitis: evidence for CX3CL1-CX3CR1-mediated immune cell recruitment.
abstract: OBJECTIVE
  Inflammatory conditions like inflammatory bowel diseases (IBD) are characterized by increased immune cell infiltration. The chemokine ligand CX3CL1 and its receptor CX3CR1 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.
  
  
  METHODS
  Acute colitis was induced by dextran sodium sulfate (DSS), and sepsis was induced by injection of lipopolysaccharide (LPS). Serum concentrations of CX3CR1 and CX3CL1 were measured by ELISA. Wild-type and CX3CR1-/-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.
  
  
  RESULTS
  CX3CR1 was upregulated in DSS colitis and LPS-induced sepsis. CX3CR1-/-mice were protected from disease severity and intestinal injury in DSS colitis, and CX3CR1 deficiency resulted in reduced rolling of leukocytes and platelets.
  
  
  CONCLUSIONS
  In the present study, we provide evidence for a crucial role of CX3CL1-CX3CR1 in experimental colitis, in particular for intestinal leukocyte recruitment during murine colitis. Our findings suggest that CX3CR1 blockade represents a potential therapeutic strategy for treatment of IBD.
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Waldeyerstraße 1, 48149, Muenster, Germany.|Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA.
authors.forename: Felix
authors.initials: F
authors.lastname: Becker
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Waldeyerstraße 1, 48149, Muenster, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Holthoff
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Waldeyerstraße 1, 48149, Muenster, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Anthoni
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Waldeyerstraße 1, 48149, Muenster, Germany.
authors.forename: Emile
authors.initials: E
authors.lastname: Rijcken
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA.
authors.forename: J Steven
authors.initials: JS
authors.lastname: Alexander
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA.
authors.forename: Felicity N E
authors.initials: FN
authors.lastname: Gavins
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Waldeyerstraße 1, 48149, Muenster, Germany.
authors.forename: H U
authors.initials: HU
authors.lastname: Spiegel
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Waldeyerstraße 1, 48149, Muenster, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Senninger
authors.affiliation: Department of General and Visceral Surgery, University Hospital Muenster, Waldeyerstraße 1, 48149, Muenster, Germany. vowinkt@ukmuenster.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Vowinkel
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D003092:Colitis / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000098:blood supply / Q000473:pathology; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D015536:Down-Regulation; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology; D020556:Neutrophil Infiltration; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D016264:Dextran Sulfate
keywords: CX3CR1; Chemokines; DSS colitis; IBD; Leukocyte adhesion