Eosinophil-derived neurotoxin and eosinophil cationic protein are key molecules for blister formation in bullous pemphigoid.

Abstract

Eosinophils, which are multifunctional leukocytes, play pivotal roles in tissue repair, immune responses against pathogens, and the pathogenesis of various diseases, including neoplasms and inflammatory conditions such as asthma and atopic dermatitis. Despite advancements in understanding eosinophil biology and recruitment, the specific roles of eosinophil granule proteins in eosinophil-associated autoimmune diseases remain incompletely understood. We sought to investigate the role of eosinophils in the pathogenesis of autoimmune blistering dermatoses. We used 2 distinct bullous pemphigoid (BP) mouse models using STAT6-deficient mice and T-box transcription factor 21-deficient mice. Eosinophil granule proteins were examined in sera and skin samples from patients with BP, and their effects on dermal-epidermal separation were assessed in vitro. STAT6-deficient mice exhibited reduced subepidermal blister formation and eosinophil infiltration in 2 BP mouse models. IgG subclass differences and complement deficiency were not involved in subepidermal blister formation in vitro. Eosinophil-derived neurotoxin and eosinophil cationic protein were substantially elevated and localized within bullous areas of skin samples from patients with BP. Importantly, these proteins significantly impaired keratinocyte adhesion in vitro. Eosinophil-derived neurotoxin and eosinophil cationic protein play a critical role in subepidermal blister formation in BP.