Division of Cellular Immunology

Prof. Dr. Hans-Reimer Rodewald

Immunfluorescence staining of lymphocytes (red) and osteoclasts (green) in bone marrow of a mouse femur.
© dkfz.de

The Division of Cellular Immunology is investigating the physiological and pathological processes of cell and organ development in the immune system as well as their immunological functions.
We generated reporter knockin mice to demonstrate that T cells and myeloid cells (e.g. dendritic cells and granulocytes) arise in the thymus from distinct progenitors under physiological conditions. Moreover, a genetic block of Notch1 signals in T cell progenitors leads to their developmental deviation to dendritic cells instead of T cells. T cell development and maturation occur in a discrete primary immunological organ, the thymus. Previous projects focused on thymus organogenesis, while in current projects we investigate functions of the transcription factor FoxN1 in thymic epithelial cells (TECs). A central area of our research is the investigation of the roles of mast cells in the immune system. Different knockout mice enabled us to characterize an enzyme of the heparin biosynthesis pathway and to elucidate the mechanism by which mast cell proteases can degrade endothelin, a blood pressure regulating factor, and detoxify structurally related snake toxins.

FUTURE OUTLOOK
Members of our team study the dynamic processes of stem cell differentiation and the plasticity of the development of mature immune cells. To this end, we develop mouse models in which stem cells and their progeny are inducibly labeled at a certain time point. Furthermore, we have generated ‘universal stem cell recipient’ mice which can be transplanted with bone marrow stem cells without the need for myeloablation, e.g. by irradiation. In another fate mapping project, we are investigating the origins of different tissue resident macrophages like osteoclasts, Kupffer cells in the liver, and microglia in the central nervous system. We are extending our thymus research toward unravelling mechanisms of acute T cell leukemia (T-ALL) development. We discovered that thymocytes undergo transformation if they non-physiologically persist in the thymus. This occurs with surprisingly high incidence if the influx of fresh progenitors into the thymus is interrupted. We hope that this new T-ALL model shall enable us to investigate the cellular and molecular mechanisms of T-ALL formation in the thymus. Comprehensive investigations of mast cell functions remain a central area of our research. We have generated a mouse mutant that is completely mast cell deficient but has an otherwise normal immune system. This new mouse represents an excellent model to clarify the question of which infections or diseases beyond allergy mast cells play immunological roles. Specifically, we will test the roles of mast cells in wound healing, asthma, response to infection and in tumor models.

Contact

Prof. Dr. Hans-Reimer Rodewald
Cellular Immunology (D110)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4120

Selected Publications

  • Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Busch K, Klapproth K, Barile M, Flossdorf M, Holland-Letz T, Schlenner SM, Reth M, Höfer T, Rodewald HR. Nature. 2015 Feb 26;518(7540):542-6. doi: 10.1038/nature14242. Epub 2015 Feb 11. PubMed PMID: 25686605.
  • Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Gomez Perdiguero E, Klapproth K, Schulz C, Busch K, Azzoni E, Crozet L, Garner H, Trouillet C, de Bruijn MF, Geissmann F, Rodewald HR. Nature. 2015 Feb 26;518(7540):547-51. doi: 10.1038/nature13989. Epub 2014 Dec 3. PubMed PMID: 25470051.
  • Cell competition is a tumour suppressor mechanism in the thymus. Martins VC, Busch K, Juraeva D, Blum C, Ludwig C, Rasche V, Lasitschka F, Mastitsky SE, Brors B, Hielscher T, Fehling HJ, Rodewald HR. Nature. 2014 May 22;509(7501):465-70. doi: 10.1038/nature13317. Epub 2014 May 14. PubMed PMID: 24828041.
  • Type 1 diabetes in NOD mice unaffected by mast cell deficiency. Gutierrez DA, Fu W, Schonefeldt S, Feyerabend TB, Ortiz-Lopez A, Lampi Y, Liston A, Mathis D, Rodewald HR. Diabetes. 2014 Nov;63(11):3827-34. doi: 10.2337/db14-0372. Epub 2014 Jun 10. PubMed PMID: 24917576.
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