Functional characterisation of MyD88-induced signal transduction during allergic reactions and infections of the skin
Final Report Abstract
In this project we analyzed the functional role of MyD88 signaling in atopic dermatitis in a mouse model using repeated epicutanous application of allergens. We could show that global deficiency of MyD88 contributes to AD pathology in a model applying OVA as allergen and to LC migration during AD initiation. Using mice, which express MyD88 exclusively in keratinocytes we were able to show that MyD88 signaling partially restores LC migration and the inflammatory reaction in the skin, but does not contribute to epidermal hyperplasia. In a second project we analyzed the allergic and inflammatory response to SEB as adjuvant of the allergic reaction. Here we could show that the allergic reaction after repeated application of SEB induces only mild allergic symptoms and partially boosts the allergic response to OVA. Deficiency of MyD88 shifts the Th1/Th2 balance towards Th2 in skin draining LN after OVA restimulation. SEB restimulation led to T cell anergy and attenuated activation of APC in skin draining LN.
Publications
- 2012. Cutting edge: Divergent cell-specific functions of MyD88 for inflammatory responses and organ injury in septic peritonitis. J. Immunol. 188: 5833-5837
Gais, P., D. Reim, G. Jusek, T. Rossmann-Bloeck, H. Weighardt, K. Pfeffer, F. Altmayr, K. P. Janssen, and B. Holzmann
(See online at https://doi.org/10.4049/jimmunol.1200038) - 2013. Langerinneg conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice. Proc. Natl. Acad. Sci. U.S.A 110: 10723-10728
Wohn, C., J. L. Ober-Blobaum, S. Haak, S. Pantelyushin, C. Cheong, S. P. Zahner, S. Onderwater, M. Kant, H. Weighardt, B. Holzmann, B. Reizis, B. Becher, E. P. Prens, and B. E. Clausen
(See online at https://doi.org/10.1073/pnas.1307569110) - 2013: Funktionelle Charakterisierung MyD88-abhängiger Signalwege bei der atopischen Dermatitis im Mausmodell. Dissertation. Universität Düsseldorf
Didovic, Sonja
- 2014. Ultraviolet-radiationinduced inflammation promotes angiotropism and metastasis in melanoma. Nature 507: 109-113
Bald, T., T. Quast, J. Landsberg, M. Rogava, N. Glodde, D. Lopez-Ramos, J. Kohlmeyer, S. Riesenberg, D. Boorn-Konijnenberg, C. Homig-Holzel, R. Reuten, B. Schadow, H. Weighardt, D. Wenzel, I. Helfrich, D. Schadendorf, W. Bloch, M. E. Bianchi, C. Lugassy, R. L. Barnhill, M. Koch, B. K. Fleischmann, I. Forster, W. Kastenmuller, W. Kolanus, M. Holzel, E. Gaffal, and T. Tuting
(See online at https://doi.org/10.1038/nature13111)
