Weighardt research group: innate immunity and extrinsic skin aging

Liaison group of the IUF and the Life & Medical Sciences Institute (LIMES) of the University of Bonn

Head of research group:
Priv.-Doz. Dr. rer. nat. Heike Weighardt tl_files/bilder/mail.gif 

Postdoc:
Dr. rer. nat. Sonja Faßbender tl_files/bilder/mail.gif

Research profile

The liaison research group “Innate immunity and extrinsic skin aging“ investigates the correlation between environmentally-induced aging processes and the innate immune system at the model organ skin. Based on these research topics the group interconnects the two main research topics of the IUF “environmentally-induced skin aging” and “environmentally-induced disturbances of the immune system”.

We investigate MyD88-induced signaling in the skin and the function of the aryl hydrocarbon receptor repressor (AhRR) in the immune system. We want to characterize the contribution of signaling pathways of the innate immune system to inflammatory and allergic reactions of the skin. Additionally, we investigate the function of MyD88 and AhRR in extrinsic aging. Furthermore, we investigate the crosstalk of TLR and AhR signaling pathways and the involvement of inflammation associated signaling pathways in aging processes.

Projects

The project “Function of the innate immune system in extrinsic skin aging” investigates the interplay of environmentally-induced aging processes with the innate immune system. We want to analyze if UVB irradiation acts as danger signal and contributes directly to skin aging by activation of the innate immune system. To achieve this, mice globally deficient for MyD88 or newly developed mouse lines that allow expression of MyD88 in specific cell populations are analyzed in a model of chronic UVB irradiation. Furthermore, we want to clarify if premature skin aging alters the efficiency of the innate immune system. Therefore, we investigate if extrinsically aged skin displays reduced skin barrier functions and whether this results in a reduced protection against pathogens. In another part of the project we want to analyze whether the AhRR contributes to extrinsic skin aging and want to explore the role of skin fibroblasts to this process. In the third project part we analyze the functional role of the transcription factor HIF1-α in UV-induced skin aging. This work is conducted in close cooperation with the labs Krutmann and Esser and is funded by the Leibniz Competition.

In the project “Function of the aryl hydrocarbon receptor repressor (AhRR) in the defense of polymicrobial and parasitic infections” we investigate the function of the AhRR in host defense and want to elucidate the interaction of the AhRR with signaling pathways of the innate immune system. This project is conducted in cooperation with Dr. Daniel Degrandi and Prof. Klaus Pfeffer from the Heinrich Heine University Düsseldorf and is funded by the Jürgen Manchot Foundation.

Cooperations

IUF internal:
Esser research group
Haarmann-Stemmann junior research group
Krutmann research group / team Unfried
Schins research group

National:
Prof. Walter Däubener, Dr. Daniel Degrandi, Prof. Klaus Pfeffer, Heinrich Heine University Düsseldorf, Prof. Bernhard Holzmann, Technical University of Munich, Prof. Thomas Tüting, University of Bonn, Dr. Marc Beyer, University of Bonn, Dr. Susanne Koch, Prof. Thomas Bieber, University of Bonn, Prof. Karin Loser, University of Münster

Selected publications

Bald T, Quast T, Landsberg J, Rogava M, Glodde N, Lopez-Ramos D, Kohlmeyer J, Riesenberg S, Boorn-Konijnenberg D, Homig-Holzel C, Reuten R, Schadow B, Weighardt H, Wenzel D, Helfrich I, Schadendorf D, Bloch W, Bianchi ME, Lugassy C, Barnhill RL, Koch M, Fleischmann BK, Forster I, Kastenmuller W, Kolanus W, Holzel M, Gaffal E, and Tuting T: Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature 507(7490): 109-113, 2014. [pubmed]

Tigges J*, Weighardt H*, Wolff S, Gotz C, Forster I, Kohne Z, Huebenthal U, Merk HF, Abel J, Haarmann-Stemmann T, Krutmann J, and Fritsche E: Aryl Hydrocarbon Receptor Repressor (AhRR) Function Revisited: Repression of CYP1 Activity in Human Skin Fibroblasts Is Not Related to AhRR Expression. J Invest Dermatol 133(1): 87-96, 2012. (*equal contribution) [pubmed] (open access)

Reim D, Westenfelder K, Kaiser-Moore S, Schlautkotter S, Holzmann B, and Weighardt H: Role of T cells for cytokine production and outcome in a model of acute septic peritonitis. Shock 31(3): 245-250, 2009. [pubmed]

Feterowski C, Emmanuilidis K, Miethke T, Gerauer K, Rump M, Ulm K, Holzmann B, and Weighardt H: Effects of functional Toll-like receptor-4 mutations on the immune response to human and experimental sepsis. Immunology 109(3): 426-431, 2003. [pubmed] (open access)

Weighardt H, Kaiser-Moore S, Vabulas RM, Kirschning CJ, Wagner H, and Holzmann B: Cutting edge: myeloid differentiation factor 88 deficiency improves resistance against sepsis caused by polymicrobial infection. J Immunol 169(6): 2823-2827, 2002. [pubmed]