Aberrant accumulation and activation of eosinophils and potentially mast cells 
(MCs) contribute to the pathogenesis of eosinophilic gastrointestinal diseases 
(EGIDs), including eosinophilic esophagitis (EoE), gastritis (EG), and 
gastroenteritis (EGE). Current treatment options, such as diet restriction and 
corticosteroids, have limited efficacy and are often inappropriate for chronic 
use. One promising new approach is to deplete eosinophils and inhibit MCs with a 
monoclonal antibody (mAb) against sialic acid-binding immunoglobulin-like lectin 
8 (Siglec-8), an inhibitory receptor selectively expressed on MCs and 
eosinophils. Here, we characterize MCs and eosinophils from human EG and EoE 
biopsies using flow cytometry and evaluate the effects of an anti-Siglec-8 mAb 
using a potentially novel Siglec-8-transgenic mouse model in which EG/EGE was 
induced by ovalbumin sensitization and intragastric challenge. MCs and 
eosinophils were significantly increased and activated in human EG and EoE 
biopsies compared with healthy controls. Similar observations were made in 
EG/EGE mice. In Siglec-8-transgenic mice, anti-Siglec-8 mAb administration 
significantly reduced eosinophils and MCs in the stomach, small intestine, and 
mesenteric lymph nodes and decreased levels of inflammatory mediators. In 
summary, these findings suggest a role for both MCs and eosinophils in EGID 
pathogenesis and support the evaluation of anti-Siglec-8 as a therapeutic 
approach that targets both eosinophils and MCs.