OX40 Expression in Eosinophils Aggravates OVA-Induced Eosinophilic Gastroenteritis

Area of Science:

• Immunology
• Gastroenterology
• Allergy

Background:

• Eosinophils drive gastrointestinal tissue damage in eosinophilic gastrointestinal diseases (EGIDs).
• The role of the OX40 pathway in eosinophil regulation within EGIDs remains unclear.
• This study investigates OX40 expression and function on eosinophils in a mouse model of eosinophilic gastroenteritis (EGE).

Purpose of the Study:

• To assess OX40 expression and its regulatory role in eosinophils during experimental EGE.
• To determine the impact of OX40 deficiency on eosinophil infiltration and inflammatory responses in the gut.
• To elucidate the signaling pathways involved in OX40-mediated eosinophil activation.

Main Methods:

• Ovalbumin (OVA)-challenged wild-type (WT) and Ox40 knockout (KO) mice were used to model EGE.
• Eosinophil infiltration, immunoglobulin production, OX40 expression, and inflammatory cytokine levels were measured in the intestine and bone marrow.
• The effect of an agonistic anti-OX40 antibody (OX86) was evaluated.

Main Results:

• OVA challenge induced significant upregulation of Ox40 mRNA, eosinophil infiltration, and Type 2 cytokine production in EGE mice.
• Ox40 deficiency ameliorated OVA-induced inflammation, reduced eosinophil infiltration, and decreased pro-inflammatory cytokine levels.
• Ox40^- eosinophils showed reduced proliferation and pro-inflammatory function, with dampened Traf2/6-related NF-κB signaling.

Conclusions:

• OX40 plays a critical role in promoting eosinophil maturation and function in OVA-induced EGE.
• The OX40 pathway, via Traf2/6-NF-κB signaling, contributes to eosinophil-driven inflammation in the gut.
• Targeting OX40 may represent a therapeutic strategy for managing eosinophilic gastrointestinal diseases.