Allergische und irritative Kontaktdermatitis in Filaggrin- und Hornerin-defizienten Mäusen

Allergic and irritant contact dermatitis in filaggrin-hornerin (FlgHrnr−/−) double-deficient mice

by Judith Maria Dettmann
Doctoral thesis
Date of Examination:2020-10-20
Date of issue:2020-10-13
Advisor:Prof. Dr. Michael P. Schön
Referee:Prof. Dr. Lutz Walter
Referee:Prof. Dr. Martin Oppermann
Persistent Address: http://dx.doi.org/10.53846/goediss-8225

 

 

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Abstract

English

The two epithelial structural proteins filaggrin (Flg) and hornerin (Hrnr) play a major role in upholding the integrity of the skin barrier function. Loss-of-function mutations in these genes cause an epidermal barrier deficiency. The missing expression of Flg and Hrnr is independently associated with impaired barrier diseases, such as atopic dermatitis. Little data are available on the association with contact dermatitis. However, with an estimated prevalence of 15-20% in the population, contact dermatitis is a socially and economically highly relevant disease. Contact dermatitis is divided into allergic (ACD) and irritant (ICD) contact dermatitis. ACD is a T cell-mediated delayed-type hypersensitivity reaction. The response depends on the activation of the adaptive immune system. ICD is a non-specific inflammatory dermatitis that involves the innate immune system only. This work investigates the relation between epidermal barrier deficiency in filaggrin-hornerin (FlgHrnr−/−) double-deficient mice and contact dermatitis. Ear thickness change was measured over a period of time as a parameter for the induced skin inflammation. FlgHrnr−/− mice showed a lower hapten threshold and therefore an elevated susceptibility to ACD. The distribution, quantity and quality of the inflammatory cell infiltration has been examined by using flow cytometry, histology and immunohistochemistry. Results suggest that a disrupted immune regulation in ACD leads to an excessive inflammation. In ICD there was no difference in ear thickness or composition of cell infiltration detected. The novel FlgHrnr−/− mouse model allows better understanding of the pathogenic mechanisms (“outside-in” hypothesis) in ACD.
Keywords: contact dermatitis; filaggrin; hornerin; skin barrier
Schlagwörter: Kontaktdermatitis; Filaggrin; Hornerin; Hautbarriere
 
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