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Veranstaltung

Semester: Wintersemester 2021

6.04.150.004 Immunology - AHR as a master regulator in cutaneous and systemic autoimmunity -  


Veranstaltungsort

  • Please contact Prof. Dr. Karin Loser for individual timing and further information (during office hours or by e-mail).

Beschreibung

Objectives and Experimental Methods:
Systemic lupus erythematosus (SLE) is an autoimmune disease and in this project, we intend to analyze the impact of aryl-hydrocarbon receptor (AHR) signalling on the pathogenic interaction of dendritic cells (DC) and T cells. For this purpose, we will make use of our unique K14-CD40L transgenic mouse model to better understand SLE-driving DC/T cell interplay with a particular focus on the role of AHR and its interaction with inflammatory signalling pathways such as NF-κB. In detail, the impact of AHR signalling on the pathophysiology of SLE in K14-CD40L tg mice shall be characterized on a molecular level. We will investigate the nuclear translocation of AHR and the interaction with its co-receptors including RelA, RelB or ARNT under autoimmune and control conditions. Additionally, the role of the endogenous aryl-hydrocarbon receptor repressor (AHRR) shall be investigated in mice (cell specifically) lacking AHR or AHRR as well as in the presence and absence of pharmacological inhibitors (MNF or GNF-351) or activators of AHR signalling (FICZ, tapinarof). Moreover, the relevance of AHR signalling for the development of pathogenic/autoreactive cells shall be characterized. Therefore, the AHR expression, localization (cytoplasm vs. nucleus) and the binding of AHR to its co-receptors will be investigated by flow and imaging cytometry in different DC subsets and T cells from mice and individuals with SLE (e.g., RNA-sequencing to characterize phenotypic and functional alterations in immune cell subsets with relevance to SLE following the modulation of the AHR pathway by using specific agonists and antagonists).

Lehrende

SWS
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Lehrsprache
englisch

empfohlenes Fachsemester
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(Stand: 16.01.2022)