NK cells and Lipoxin A4 promote resolution of eosinophilic inflammation
after nasal allergen challenge
Background: Resolution of inflammation is now recognized as a tightly
regulated and active process. Lipoxins (LX) are lead members of a larger
family of specialized pro-resolving mediators with unique
anti-inflammatory and pro-resolving properties. Recent studies
implicated natural killer (NK) cells in the resolution of allergic
airway inflammation, notably in promoting eosinophil apoptosis. The aim
of the study was to better understand the pro-resolving actions of NK
cells and LXA4 during allergic eosinophilic airway inflammation.
Methods: 20 subjects with grass pollen allergic rhinitis were included.
A nasal provocation test with either a single grass pollen allergen
threshold dose or diluent was used. Nasal lavage fluid and cells were
collected at baseline and at different time points after challenge. For
in vitro assays, eosinophils were incubated with NK cells. Results: We
observed that NK cells were recruited to the nasal mucosa shortly after
the initiation of the allergic inflammatory response. This recruitment
correlated with eosinophilic inflammation. In vitro assays demonstrated
that direct contact and a combined action of CD56bright and CD56dim NK
cells were needed to promote autologous eosinophil apoptosis. We
furthermore observed that local LXA4 production correlated with the peak
of neutrophil nasal mucosal infiltration, suggesting a potential role of
neutrophils in LXA4 biosynthesis during the early phase of the allergic
inflammatory response. Last, LXA4 appeared as essential to inhibit the
in vitro release of eosinophil superoxide triggered by NK cells.
Conclusion: Together, these findings indicate a synergistic role for NK
cells and LXA4 in the resolution of allergic eosinophilic inflammation.