Natural Killer Cell Deficit Aggravates Eosinophilic Chronic Rhinosinusitis in a Murine Model

Abstract

RationaleChronic rhinosinusitis (CRS) is a multifactorial inflammatory disease of the nasal and paranasal cavities. Defective immune functions may contribute to the chronic inflammatory state in this disorder. Recently, it has been reported that CRS patients show the impaired function of natural killer (NK) cells, especially in recalcitrant CRS associated with asthma and eosinophilia. We investigated the role of NK cells in mucosal and systemic, particularly eosinophilic, inflammation in an allergic CRS (ACRS) mouse model.MethodsMice sensitized to ovalbumin (OVA) by intraperitoneal injection received nasal challenges with OVA for 5 weeks. NK cell depletion was achieved by intraperitoneal injections of anti-asialo ganglio-N-tetraosylceramide antibodies 10 days before OVA sensitization and every 5 days until sacrifice. Sinonasal complex samples were evaluated histologically, and IL-4, IL-5, IL-13, IFN-γ, IL-8, and eotaxin were measured in nasal lavage fluid. A differential white blood cell count was also performed.ResultsACRS mice showed significantly increased eosinophilic inflammation in sinonasal mucosa, elevated levels of IL-4, IL-5, IL-13, IFN-γ, and eotaxin in nasal lavage fluid, and peripheral blood eosinophilia compared with control mice. The depletion of NK cells induced more prominent eosinophilic inflammation, increased secretion of IL-5, and peripheral blood eosinophilia in ACRS mice.ConclusionsThese results presented that the depletion of NK cells aggravates allergen-induced sinonasal eosinophilic inflammation, suggesting that impaired NK cell activity may be an aggravating factor in eosinophilic CRS. RationaleChronic rhinosinusitis (CRS) is a multifactorial inflammatory disease of the nasal and paranasal cavities. Defective immune functions may contribute to the chronic inflammatory state in this disorder. Recently, it has been reported that CRS patients show the impaired function of natural killer (NK) cells, especially in recalcitrant CRS associated with asthma and eosinophilia. We investigated the role of NK cells in mucosal and systemic, particularly eosinophilic, inflammation in an allergic CRS (ACRS) mouse model. Chronic rhinosinusitis (CRS) is a multifactorial inflammatory disease of the nasal and paranasal cavities. Defective immune functions may contribute to the chronic inflammatory state in this disorder. Recently, it has been reported that CRS patients show the impaired function of natural killer (NK) cells, especially in recalcitrant CRS associated with asthma and eosinophilia. We investigated the role of NK cells in mucosal and systemic, particularly eosinophilic, inflammation in an allergic CRS (ACRS) mouse model. MethodsMice sensitized to ovalbumin (OVA) by intraperitoneal injection received nasal challenges with OVA for 5 weeks. NK cell depletion was achieved by intraperitoneal injections of anti-asialo ganglio-N-tetraosylceramide antibodies 10 days before OVA sensitization and every 5 days until sacrifice. Sinonasal complex samples were evaluated histologically, and IL-4, IL-5, IL-13, IFN-γ, IL-8, and eotaxin were measured in nasal lavage fluid. A differential white blood cell count was also performed. Mice sensitized to ovalbumin (OVA) by intraperitoneal injection received nasal challenges with OVA for 5 weeks. NK cell depletion was achieved by intraperitoneal injections of anti-asialo ganglio-N-tetraosylceramide antibodies 10 days before OVA sensitization and every 5 days until sacrifice. Sinonasal complex samples were evaluated histologically, and IL-4, IL-5, IL-13, IFN-γ, IL-8, and eotaxin were measured in nasal lavage fluid. A differential white blood cell count was also performed. ResultsACRS mice showed significantly increased eosinophilic inflammation in sinonasal mucosa, elevated levels of IL-4, IL-5, IL-13, IFN-γ, and eotaxin in nasal lavage fluid, and peripheral blood eosinophilia compared with control mice. The depletion of NK cells induced more prominent eosinophilic inflammation, increased secretion of IL-5, and peripheral blood eosinophilia in ACRS mice. ACRS mice showed significantly increased eosinophilic inflammation in sinonasal mucosa, elevated levels of IL-4, IL-5, IL-13, IFN-γ, and eotaxin in nasal lavage fluid, and peripheral blood eosinophilia compared with control mice. The depletion of NK cells induced more prominent eosinophilic inflammation, increased secretion of IL-5, and peripheral blood eosinophilia in ACRS mice. ConclusionsThese results presented that the depletion of NK cells aggravates allergen-induced sinonasal eosinophilic inflammation, suggesting that impaired NK cell activity may be an aggravating factor in eosinophilic CRS. These results presented that the depletion of NK cells aggravates allergen-induced sinonasal eosinophilic inflammation, suggesting that impaired NK cell activity may be an aggravating factor in eosinophilic CRS.