Interleukin 5 dependent inflammatory eosinophil subtype involved in
allergic insect bite hypersensitivity of horses
Abstract
Eosinophils are known to play a crucial role in equine insect bite
hypersensitivity (IBH), an allergic and pruritic dermatitis. Given the
relevant role of eosinophils in disease pathology, a virus-like particle
(VLP)-based vaccination targeting equine Interleukin (eIL)-5 has been
shown to significantly reduce eosinophil levels in the blood and hence
reduced IBH symptoms in horses. The aim of the present study was to
assess the presence of different eosinophil subtypes in horses, describe
characteristics of these subtypes and evaluate the effect of
eIL-5-CuMVTT vaccination on these subtypes. The study involved healthy
horses, untreated IBH horses, eIL-5-CuMVTT vaccinated and
placebo-treated IBH horses, assessed in parallel during the same IBH
season. For the first time, this study showed presence of two distinct
eosinophil subtypes in horses. An inflammatory subtype was associated
with allergy, which had a significantly larger cell size, increased
intracellular granula and higher surface expression of the integrin
CD49f hi. Regulatory steady-state eosinophils were
identified in healthy blood sample and with smaller relative cell size,
had less intracellular granula and significantly lower levels of surface
integrin CD49f dim. The eIL-5-CuMVTT vaccination
significantly reduced eosinophil levels in the blood throughout the
whole IBH season, indicating IL-5-dependence of inflammatory
eosinophils. However, it did not alter the phenotype of the remaining
cells. The mechanism of action of vaccination likely acts by limiting
availability of eosinophils in the blood for extravasation into the
skin.