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.
| Original language | English |
|---|---|
| Pages (from-to) | 1016-1026 |
| Number of pages | 11 |
| Journal | Mucosal immunology |
| Volume | 6 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Sept 2013 |
Bibliographical note
Funding Information:The Alimentary Pharmabiotic Center is a research center funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan. We and our work are supported in part by SFI grant numbers: 02/CE/B124 and 07/CE/B1368. We thank Professor Wayne Yokoyama, Washington University School of Medicine, St Louis, USA, for the kind gift of NKD mice and critical reading of the manuscript.
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology