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

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Abstract

Purpose

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.

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Acknowledgements

The authors thank Ludgera Weber-Koberg for excellent technical assistance.

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Authors and Affiliations

  1. Department of General and Visceral Surgery, University Hospital Muenster, Waldeyerstraße 1, 48149, Muenster, Germany

    Felix Becker, Christina Holthoff, Christoph Anthoni, Emile Rijcken, HU Spiegel, Norbert Senninger & Thorsten Vowinkel

  2. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA

    Felix Becker, J. Steven Alexander & Felicity N. E. Gavins

Authors
  1. Felix Becker
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  2. Christina Holthoff
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  3. Christoph Anthoni
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  7. HU Spiegel
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  9. Thorsten Vowinkel
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Corresponding author

Correspondence to Thorsten Vowinkel.

Ethics declarations

All animal protocols were approved by the animal subjects committee, University of Muenster (LANUV permit number: 8.87–50.10.36.09.037) and conducted as outlined by the German Animal Welfare Law.

Grants

This research was funded by a grant (VO 998/3-1) from the German Research Foundation (DFG) to T. Vowinkel.

Conflict of interest

The authors declare that they have no conflict of interest.

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Becker, F., Holthoff, C., Anthoni, C. et al. Downregulation of CX3CR1 ameliorates experimental colitis: evidence for CX3CL1-CX3CR1-mediated immune cell recruitment. Int J Colorectal Dis 32, 315–324 (2017). https://doi.org/10.1007/s00384-016-2735-y

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  • DOI: https://doi.org/10.1007/s00384-016-2735-y

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