Dr. Johannes E. Gessner
Department of Clinical Immunology
Fc receptors in inflammation and autoimmune disease Dissection of genetic factors is a major focus of research in inflammation and autoimmune disorders and has been greatly facilitated by the characterization of animal models of disease. Gene targeting of the activatory FcgRIII protects mice from antibody- and immune complex-mediated inflammation, which suggests that this IgG Fc receptor is able to trigger the effector arm of autoimmune diseases. On the other hand, direct in vivo studies on the clinical relevance of FcgRIII in humans are limited. In the future, humanized FcgRIII mouse models in combination with targeting FcgRIII binding sites are required to establish the significance of FcgRIII blockade as an immunotherapeutic modality for human disease.
A) Inflammatory disease of the lung/ gene expression profile analysis. To identify mediators in the development of FcgRIII-triggered inflammation, gene expression profile analysis of knock-out and control mice will be performed using approaches such as PCR select and microarray.
B) Autoimmune disease / generation of FcgR (-/-) mice. FcgRI and FcgRIII expression in the kidney contribute to the development of glomerulonephritis. BXSB chimeric mice lacking these two Fc receptors on their parenchymal cells only will be generated and analysed.
C) Analysis of humanized mice / new therapeutic approaches. Humanized FcgRIII tg/ (-/-) mice are used as a model system to test the efficiency of human-specific FcgRIII-blocking reagents in the treatment of experimentally induced diseases.