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PLoS One. 2014 Jul 3;9(7):e101622. doi: 10.1371/journal.pone.0101622. eCollection 2014.

The role of CXCR3 in DSS-induced colitis.

Author information

1
Discipline of Pathology, Bosch Institute and School of Medical Sciences, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
2
Centre for Vascular Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, NSW, Australia.
3
Discipline of Pathology, Bosch Institute and School of Medical Sciences, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Sydney Institute of Emerging infectious diseases and Biosecurity (SEIB), Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

Abstract

Inflammatory bowel disease (IBD) is a group of disorders that are characterized by chronic, uncontrolled inflammation in the intestinal mucosa. Although the aetiopathogenesis is poorly understood, it is widely believed that IBD stems from a dysregulated immune response towards otherwise harmless commensal bacteria. Chemokines induce and enhance inflammation through their involvement in cellular trafficking. Reducing or limiting the influx of these proinflammatory cells has previously been demonstrated to attenuate inflammation. CXCR3, a chemokine receptor in the CXC family that binds to CXCL9, CXCL10 and CXCL11, is strongly overexpressed in the intestinal mucosa of IBD patients. We hypothesised that CXCR3 KO mice would have impaired cellular trafficking, thereby reducing the inflammatory insult by proinflammatory cell and attenuating the course of colitis. To investigate the role of CXCR3 in the progression of colitis, the development of dextran sulfate sodium (DSS)-induced colitis was investigated in CXCR3-/- mice over 9 days. This study demonstrated attenuated DSS-induced colitis in CXCR3-/- mice at both the macroscopic and microscopic level. Reduced colitis correlated with lower recruitment of neutrophils (p = 0.0018), as well as decreased production of IL-6 (p<0.0001), TNF (p = 0.0038), and IFN-γ (p = 0.0478). Overall, our results suggest that CXCR3 plays an important role in recruiting proinflammatory cells to the colon during colitis and that CXCR3 may be a therapeutic target to reduce the influx of proinflammatory cells in the inflamed colon.

PMID:
24992040
PMCID:
PMC4081590
DOI:
10.1371/journal.pone.0101622
[Indexed for MEDLINE]
Free PMC Article

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