Introduction
Allergic airway diseases, such as rhinitis and asthma, are one of the most common chronic inflammatory respiratory diseases in the world (1). The pathophysiology of allergic airway diseases involves a typical immunoglobulin (Ig) E-mediated type 2 immune response triggered in sensitized subjects following inhalation of aeroallergens with subsequent eosinophilic infiltration of the respiratory mucosa (2). Although the mechanisms underlying the pathology and treatment of allergic airway inflammation have been widely studied, many aspects remain unclear, notably how allergic inflammation effectively resolves in the airways.
The resolution of inflammation is now recognized as a tightly regulated and active process (3). From the apoptosis and clearance by myeloid cells of activated inflammatory cells to the release of pro-resolving molecules, resolution enables inflamed tissues to return to homeostasis. Non-resolving inflammation is suspected as a key factor in the pathogenesis of numerous chronic inflammatory diseases, including allergic rhinitis and asthma (4).
Lipoxins (LX) are lead members of a larger family of specialized pro-resolving mediators with unique anti-inflammatory and pro-resolving properties (5). LX derive from essential fatty acids and are generatedvia biosynthetic routes engaged during cell-cell interactions (for example when infiltrating neutrophils interact with tissue-resident cells in inflamed target organs) (5). Previous animal studies showed that LX can decrease allergic inflammation (6, 7). Moreover, low lipoxin production has been observed in patients with severe and uncontrolled asthma (8, 9).
Natural Killer (NK) cells are well-known players in the control and elimination of virally-infected or cancer cells (10). But several animal studies also implicated NK cells in the resolution of allergic inflammation, notably in dampening eosinophilic inflammation (11). Previous data demonstrated that NK cells are able to induce the apoptosis of human autologous eosinophils in vitro (12, 13). In contrast, a potential activator effect of NK cells on eosinophils has also been reported, notably by increasing reactive oxygen species (ROS) expression by eosinophils in co-cultures (13).
The aim of the study was to better understand the pro-resolving actions of NK cells and LXA4 during a self-limited allergic respiratory inflammatory response by using a standardized nasal allergen provocation test with a single threshold dose. We were able to identify a synergistic role for NK cells and LXA4 in mediating resolution of allergic eosinophilic inflammation.