Dokument: Interleukin-26: A cytokine at the interface between innate and adaptive immunity
| Titel: | Interleukin-26: A cytokine at the interface between innate and adaptive immunity | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=49776 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20200617-104330-7 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Hawerkamp, Heike [Autor] | |||||||
| Dateien: |
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| Beitragende: | Priv.-Doz. Dr. Meller, Stephan [Gutachter] Prof. Dr. Hegemann, J. H. [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Interleukin-26 (IL-26) is a cytokine mainly secreted from TH17 cells with multifaceted characteristics. IL-26 signals through a receptor heterodimer consisting of IL-20R1 and IL-10R2. This unique heterodimeric combination is only found on a few cell types, such as epithelial cell. In these cells, such as keratinocytes or colon cells, IL-26 signals via the STAT pathway and elicits the secretion of pro-inflammatory IL-8. Investigating the molecular properties of IL-26, it was revealed that IL-26 is highly cationic and has an amphipathic structure, a phenomenon where charged amino acids cluster within the molecule. This amphipathic structure is common among antimicrobial peptides. Similar to antimicrobial peptides, IL-26 is able to directly kill microorganisms. Besides this impact on innate immunity, IL-26 also plays a role in autoimmunity. IL-26’s cationic surface allows for binding to human self-DNA, which then gets transferred into immune cells that erroneously induce an antiviral immune response.
In this project, we characterize the role of IL-26 in different skin diseases via gene expression analysis. Furthermore, we closely investigate the binding partners of IL-26 on the surface of different microbes, such as LPS and LTA, using microscale thermophoresis, including a broad investigation of IL-26’s potential in killing mycobacteria, as well as its role in tuberculosis. Additionally, the investigation on the binding of IL-26 to anionic compounds is extended to RNA, and the subsequent effects of IL-26/RNA complexes on the respective immune cells, such as dendritic cells, were elucidated. As immune cells need to be attracted to such inflammatory sites, we set off to uncover some chemokine ligand and receptor patterns involved in immune cell recruitment in the presence of IL-26 and IL-26 nucleic acid complexes. Seeing that immune cells respond to IL-26 in absence of the IL-26 receptor, we investigate suitable surface molecules that might transmit signals upon IL-26 binding. Another part of this project aims to unveil the effects of IL-26 under reducing conditions that resemble the physiological state during inflammation. Here, we compare the oxidized IL-26 to its reduced counterpart without disulphide bonds, and examined the effects on protein binding partners as well as on stimulatory capacity of immune cells. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 17.06.2020 | |||||||
| Dateien geändert am: | 17.06.2020 | |||||||
| Promotionsantrag am: | 23.11.2018 | |||||||
| Datum der Promotion: | 24.04.2019 |
