Final Report Summary - MAST-CELL-FUNCTIONS (Genetically defined and selectively mast cell-deficient mouse model to unravel the immunological roles of mast cells)
Between 2000 and 2009, we had generated a series of mouse mutants to study mast cell development and functions in vivo. One of these mice (Cpa3-Cre mice) was completely devoid of mast cells in all tissues that we studies. Functionally, these mutants were fully protected from allergic diseases. But surprisingly, other immune functions were completely normal in the absence of mast cells. This was perplexing and we began a systematic search for diseases which were either ameliorated or worsened by mast cells. In this 6-year research project, we studied with the help of expert collaborators functions of mast cells in host defense against venom toxins, bacteria (sepsis), protozoa (Leishmania major) and helminthes (Strongyloides ratti), mast cells in autoimmunity (EAE, arthritis, type1 diabetes), mast cells in immune metabolism, mast cells in the skin, and mast cells in tumor biology. For almost all of these conditions there were earlier reports that had suggested important roles for mast cells. Despite these claims, with the exception of protection from some venoms, and impaired immunity to some helminthes, we could not identify an impact of mast cells on these highly diverse pathological conditions. As a result, it remains enigmatic what mast cells are good for, at least as far as it is measurable in the laboratory. Nevertheless, the development of new and conclusive mouse mutants provided us the technology to re-address long standing questions in immunology in a rigorous manner. This shall help the field to identify new leads to follow in the quest to discover the physiological function of mast cells in vivo.