de Graauw, Elisabeth Louisa Maria; Sitaru, Cassian; Horn, Michael Peter; Borradori, Luca; Yousefi, Shida; Simon, Hans-Uwe; Simon, Dagmar (2017). Evidence for a role of eosinophils in blister formation in bullous pemphigoid. Allergy, 72(7), pp. 1105-1113. Wiley-Blackwell 10.1111/all.13131
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BACKGROUND
Bullous pemphigoid (BP) is an autoimmune bullous disease of the skin characterized by subepidermal blister formation due to tissue-bound and circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. Although eosinophils and their toxic mediators are found abundantly in BP lesions, their role in blister formation has remained unclear.
OBJECTIVE
To investigate the role of eosinophils in the pathogenesis of BP with a specific focus on blister formation and to define conditions inducing dermal-epidermal separation (DES).
METHODS
In an ex vivo human model of BP, normal human skin cryosections were incubated with purified human peripheral blood eosinophils with or without activation in the presence or absence of BP autoantibodies, brefeldin A, diphenyleneiodonium (DPI), DNase, or blocking F(ab')2 fragments to CD16, CD18, CD32 and CD64. DES was assessed by light microscopy studies and quantified using Fiji software.
RESULTS
Following activation with IL-5 and in the presence of BP autoantibodies, eosinophils induced separation along the dermal-epidermal junction of ex vivo skin. DES was significantly reduced by blocking any of the following: Fcγ receptor binding (p=0.048), eosinophil adhesion (p=0.046), reactive oxygen species (ROS) production (p=0.002), degranulation (p<0.0001), or eosinophil extracellular trap (EET) formation (p=0.048).
CONCLUSIONS
Our results provide evidence that IL-5-activated eosinophils directly contribute to BP blister formation in the presence of BP autoantibodies. DES by IL-5-activated eosinophils depends on adhesion and Fcγ receptor activation, requires elevated ROS production and degranulation, and involves EET formation. Thus, targeting eosinophils may be a promising therapeutic approach for BP. This article is protected by copyright. All rights reserved.
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