Natural Killer Cell Deficits Aggravate Allergic Rhinosinusitis in a Murine Model

Abstract

Objective: Defective innate immune functions can contribute to chronic rhinosinusitis (RS). Recently, it has been reported that chronic RS patients show impaired function of natural killer (NK) cells. We investigated the role of NK cells in eosinophilic inflammation in an allergic RS mouse model. Methods: 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 (ASGM1) antibodies 10 days before OVA sensitization and every 5 days thereafter until sacrifice. Sinonasal complex samples were evaluated histologically, and IL-4, IL-5, IL-13, IFN-γ, MIP-2, and eotaxin levels were measured in the nasal lavage fluid. Differential white blood cell counts were also obtained. Results: Allergic RS mice showed significantly more eosinophilic inflammation in the sinonasal mucosa, elevated levels of IL-4, IL-5, IL-13, and eotaxin in the nasal lavage fluid, and peripheral blood eosinophilia compared to control mice. The depletion of NK cells by anti-ASGM1 treatment induced more prominent eosinophilic inflammation and increased secretion of IL-5 and peripheral blood eosinophilia in allergic RS mice. Conclusion: The depletion of NK cells aggravates allergen-induced sinonasal eosinophilic inflammation, suggesting that impaired NK cell activity may be an exacerbating factor in eosinophilic chronic RS.

Novel innate and adaptive lymphocytes: The new players in the pathogenesis of inflammatory upper airway diseases

“…13 The IL-22-secreting NK22 cells might have a role in the protection of epithelial cell barriers. 14 19,20 Although the percentage of CD56 + NK cells in peripheral blood mononuclear cells (PBMCs) was increased in AR patients, 21 the percentage of CD56 bright subpopulation in total NK cells has been reported to be decreased in AR patients, which might contribute to reduced IFN-c production. 22 ILC1s (non-NK) are analogous to Th1 cells.…”

“…Kim et al showed that peripheral NK cells from patients with CRS had an impaired effector function reflected by decreased ability to degranulate and to produce IFN‐γ and TNF‐α. This defect was possibly induced by prostaglandin D2 (PGD2), contributed to reduced eosinophil apoptosis, and associated with disease severity in patients with CRS . Although the percentage of CD56 + NK cells in peripheral blood mononuclear cells (PBMCs) was increased in AR patients, the percentage of CD56 bright subpopulation in total NK cells has been reported to be decreased in AR patients, which might contribute to reduced IFN‐γ production .…”

Role of Natural Killer Cells in Airway Inflammation

“…Natural killer (NK) cells are innate lymphocytes with natural cytotoxicity against infected and cancer cells located in non-lymphoid as well as lymphoid organs. 1 2 3 4 5 NK cells can be subdivided into phenotypically and functionally different populations on the basis of their relative expression of CD56 and CD16 surface markers. More differentiated CD56 dim CD16 + NK cells comprise up to 90% of the peripheral blood NK cells and contain high levels of perforin, granzymes and cytolytic granules.…”

“…NK cells control chronic inflammation in airways and act rapidly to eliminate pathogens in acute respiratory infection. 1 2 3 4 5 Asthma and chronic obstructive pulmonary disease (COPD) in the lower airway as well as allergic rhinitis (AR) and chronic rhinosinusitis (CRS) in the upper airway exhibit both similar and different histological and immunological characteristics. 10 11 This review focuses on the role of NK cells in chronic inflammatory airway diseases.…”

“…NK cell depletion before immunization increased eosinophilic infiltration, IL-5 secretion and peripheral blood eosinophilia in an OVA-induced allergic rhinosinusitis mouse model. 4 …”