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.