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Semester: Wintersemester 2021 Immunology - AHR as a master regulator in cutaneous and systemic autoimmunity -  


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


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).




empfohlenes Fachsemester

(Stand: 16.01.2022)