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Updated: May 14, 2026
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Natural killer cells protect mice from DSS-induced colitis by regulating neutrophil function via the NKG2A receptor
L J Hall1, C T Murphy, A Quinlan
1Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland. Lindsay.Hall@uea.ac.uk
Abstract:
Natural killer (NK) cells are traditionally considered in the context of tumor surveillance and infection defense but their role in chronic inflammatory disorders such as inflammatory bowel disease is less clear. Here, we investigated the role of NK cells in dextran sodium sulfate (DSS)-induced colitis in mice. Depletion of NK cells impairs the survival of mice with colitis and is linked with dramatic increases in colonic damage, leukocyte infiltration, and pro-inflammatory profiles. Mice depleted of NK cells had increased numbers of neutrophils in colons and mesenteric lymph nodes, compared with control mice, in addition to acquiring a hyper-activation status. In vitro and in vivo studies demonstrate that NK cells downregulate pro-inflammatory functions of activated neutrophils, including reactive oxygen species and cytokine production, by direct cell-to-cell contact involving the NK cell-inhibitory receptor NKG2A. Our results indicate an immunoregulatory mechanism of action of NK cells attenuating DSS-induced colitis neutrophil-mediated inflammation and tissue injury via NKG2A-dependent mechanisms.
Insights
Natural killer (NK) cells regulate inflammation in inflammatory bowel disease. These cells dampen neutrophil-driven tissue injury and inflammation in dextran sodium sulfate-induced colitis via NKG2A-dependent mechanisms.
Area of Science:
- Immunology
- Gastroenterology
Background:
- Natural killer (NK) cells are primarily known for tumor surveillance and infection defense.
- Their role in chronic inflammatory disorders like inflammatory bowel disease (IBD) remains less understood.
Purpose of the Study:
- To investigate the function of NK cells in dextran sodium sulfate (DSS)-induced colitis, a model for IBD.
- To elucidate the mechanisms by which NK cells modulate inflammation and tissue damage in this model.
Main Methods:
- Utilized a mouse model of DSS-induced colitis.
- Depleted NK cells to assess their impact on disease severity.
- Conducted in vitro and in vivo experiments to analyze neutrophil activation and NK cell interactions.
- Investigated the role of the NKG2A receptor in NK cell-mediated regulation.
Main Results:
- Depletion of NK cells exacerbated colitis, leading to increased colonic damage and leukocyte infiltration.
- Mice lacking NK cells showed elevated neutrophil numbers and hyper-activation in the colon and mesenteric lymph nodes.
- NK cells directly suppressed neutrophil pro-inflammatory functions, including reactive oxygen species and cytokine production.
- This suppression was mediated by cell-to-cell contact involving the NKG2A receptor.
Conclusions:
- NK cells play a crucial immunoregulatory role in attenuating DSS-induced colitis.
- NK cells mitigate neutrophil-driven inflammation and tissue injury through NKG2A-dependent mechanisms.
- These findings highlight a novel therapeutic target for managing inflammatory bowel disease.
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