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Authors: Brand, Anna
Title: Role of E-cadherin in Langerhans cell homeostasis & Analysis of an IL-17A-driven psoriasis mouse model
Online publication date: 17-Feb-2020
Language: english
Abstract: In the first part of this thesis we analyzed the cell adhesion molecule E-cadherin, which is a major component of adherens junctions and marker for LC in the epidermis. Here, LC attach to the surrounding KC via homophilic E-cadherin binding and downregulation of E-cadherin coincides with LC migration. To date, it is unknown whether E-cadherin is just a marker identifying LC or whether it regulates LC homeostasis and function. Therefore, we investigated the role of E-cadherin cell adhesion and signaling in DC in vivo, in mice with conditional knockout of E-cadherin in all CD11c+ cells (CD11c-Ecaddel). In the absence of E-cadherin, LC numbers in CD11c-Ecaddel and control mice were comparable and stable, even in aged animals. Intriguingly, E-cadherin deficient LC displayed a more rounded cell body and fewer dendrites compared to controls. Nevertheless, maturation and migration of E-cadherin-deficient LC were not altered, neither under steady state nor inflammatory conditions. In conclusion, these data demonstrate that E-cadherin is dispensable to maintain LC in the epidermis and does not regulate LC maturation, migration nor function. In the second part of this thesis we developed a chronic psoriasis mouse model by targeting IL-17A expression to CD11c+ cells (CD11c-IL17Aind). Patients with severe psoriasis suffer from an increased risk of cardiovascular mortality. Indeed, we demonstrated that overexpression of IL-17A in CD11c+ cells leads to psoriasis-like skin disease and vascular dysfunction. Interestingly, systemic IL-17A serum level correlated with the severity of skin and vascular phenotype. In addition, we showed that neutralization of IL-17A can protect CD11c-IL17Aind mice from the concurrent development of skin lesions and cardiovascular disease. This was manifested by abolished psoriatic plaque formation and an improved vascular function. Our data highlight the pivotal role of IL-17A linking the development of skin lesions and vascular disease in psoriasis. Therefore, CD11c-IL17Aind mice represent a novel mouse model to investigate the correlation between IL-17A mediated chronic skin disease and vascular dysfunction as well as to validate new therapeutic targets.
DDC: 000 Allgemeines
000 Generalities
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
URN: urn:nbn:de:hebis:77-diss-1000034106
Version: Original work
Publication type: Dissertation
License: In Copyright
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Extent: V, 106 Blätter
Appears in collections:JGU-Publikationen

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