Characterization of inflammation-induced extramedullary myelopoiesis and its contribution to the myeloid cell population.
Immunology
Virology
Final Report Abstract
Usually, the bone marrow is the primary site of myeloid immune cell production (myelopoiesis). However, during infection and inflammation, myelopoiesis can occur in tissues outside of the bone marrow, e.g. in spleen. This phenomenon is called extramedullary myelopoiesis. The first aim of this project was to elucidate cellular and molecular mechanisms that govern extramedullary myelopoiesis. Candidate cells and genes were identified before using cell depletion methods and small molecule inhibitors. However, testing in genetic mouse models could not confirm a role for these candidates in the regulation of extramedullary myelopoiesis. The second aim was to evaluate the contribution of extramedullary myelopoiesis to immunity. To this end it is essential to separate the contribution of the bone marrow from the contribution of the spleen. Surgical methods were not sufficient to address this question, and until the end of 2015 no genetic model specifically targeting the hematopoietic niche in the spleen was available. While studying myeloid cells in peripheral blood and organs, I made the interesting observation that their numbers correlate with the caloric value of the food ingested. It was known that high calorie diets fuel inflammatory processes, whereas caloric restriction could improve inflammatory diseases and autoimmune disorders, but the mechanism was poorly understood. Therefore, I focused my research on the question how calorie intake regulated immune cell populations. I found out that the major transcriptional regulator in the response to low calorie intake not only governed the metabolic adaptation but also inhibited cell egress from the bone marrow. Hence, our dietary habits might correlate with the individual risk for inflammatory and autoimmune diseases. In my future role as principal investigator I will continue to study how food modulates our immune system.
