Neutrophil Extracellular Traps (NETs) in der Interleukin-23-induzierten psoriasiformen Dermatitis
Neutrophil Extracellular Traps (NETs) in Interleukin-23-mediated psoriasis-like skin inflammation
von Veit Steffen Manzke
Datum der mündl. Prüfung:2021-07-27
Erschienen:2021-07-14
Betreuer:Prof. Dr. Michael P. Schön
Gutachter:Prof. Dr. Lutz Walter
Gutachter:Prof. Dr. Ralf Dressel
Dateien
Name:Manzke Dissertation SUB.pdf
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Format:PDF
Zusammenfassung
Englisch
Psoriasis is a chronic recurrent inflammatory disease of the skin and joints, often associated with significant morbidity. In spite of its clinical importance, the pathogenesis of psoriasis is not fully understood. Recently, it was discovered that Neutrophil Extracellular Traps (NETs) may be involved in the inflammatory process of this disease, as these networks of chromatin and antimicrobial peptides, expelled by neutrophilic granulocytes, can be found in psoriatic plaques and are colocalized with Interleukin 17, a keyplayer in the signal pathway of Psoriasis. Therefore, the TLR dependency of the Netosis, triggered by different activators of the Netosis, was investigated. There was no significant difference within the knock-out-mice. Furthermore a mouse model of psoriasis-like skin inflammation was established, using intradermal injections of IL-23 in Bl6 mice. NETs were shown in the early phase (day 5) of the chronic inflammation, whereas they aren´t significantly present in later phases (day 10). Proceeding this results, the therapeutical, systemic hydrolysis of DNA with DNase 1 led to a decrease in the presence of NETs, as well as the clinical reduction of inflammation. In addition to that, it seems that the NETs are locally restricted. An increased systemic NETosis during the inflammatory process wasn´t shown. The systemic application of DNase 1 doesn´t reduce the free DNA in control mice.
Keywords: Neutrophil; Extracellular; Traps; NET; NETosis; Psoriasis; Interleukin-23; psoriasis-like; inflammation; NETs