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
Postdoc:
Dr. rer. nat. Sonja Faßbender
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]