title: Natural killer cells protect mice from DSS-induced colitis by regulating neutrophil function via the NKG2A receptor.
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.
authors: Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland. Lindsay.Hall@uea.ac.uk
authors: L J
authors: LJ
authors: Hall
authors: C T
authors: CT
authors: Murphy
authors: A
authors: A
authors: Quinlan
authors: G
authors: G
authors: Hurley
authors: F
authors: F
authors: Shanahan
authors: K
authors: K
authors: Nally
authors: S
authors: S
authors: Melgar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000008:administration & dosage; D018836:Inflammation Mediators / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D055654:NK Cell Lectin-Like Receptor Subfamily C; D017382:Reactive Oxygen Species; D016264:Dextran Sulfate