Evidence for a role of eosinophils in blister formation in bullous pemphigoid.

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

de Graauw, Elisabeth Louisa Maria; Horn, Michael Peter; Borradori, Luca; Yousefi, Shida; Simon, Hans-Uwe and Simon, Dagmar

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0105-4538

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Jana Berger

Date Deposited:

11 Sep 2017 10:11

Last Modified:

01 Aug 2018 02:30

Publisher DOI:

10.1111/all.13131

PubMed ID:

28135772

Uncontrolled Keywords:

BP autoantibody adhesion blister formation bullous pemphigoid degranulation eosinophils interleukin-5

BORIS DOI:

10.7892/boris.95344

URI:

https://boris.unibe.ch/id/eprint/95344

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