The impact of immune activation on hematopoiesis
This research line focuses on the cellular and molecular mechanisms by which the activated immune system can modulate the intricate process of hematopoiesis in the bone marrow. We have found that activated T cells can directly influence differentiation of progenitor cells at a variety of different lineages. As such, we have found that T cell-derived IFNγ negatively affects differentiation of B cells, neutrophils and erythroid cells, whereas it enhances the formation of monocytes. Moreover, we also found that IFNγ has a direct effect on hematopoietic stem cells (HSCs), as it stimulates the differentiation capacity of these cells, which negatively affects their self-renewal ability. Furthermore, we found that a particular subset of memory CD8 T cells can also influence HSC function in an IFNγ-independent manner.
Using both in vitro and in vivo models, we focus on the molecular mechanism by which several types of immune cells are able to influence the function of stem and progenitor cells. With the approach chosen for this line of research, we operate at the crossroads of hematology and immunology. These two disciplines clearly have a direct affiliation, but are infrequently combined in fundamental research. With this approach, we aim to give insight in a, so far, unexplored aspect of hematopoietic regulation, which will contribute to a better understanding of the consequences of immune activation.
Key publications
- De Bruin AM, Buitenhuis M, van der Sluijs KF, van Gisbergen KP, Boon L, Nolte MA. Eosinophil differentiation in the bone marrow is inhibited by T cell-derived IFN-gamma. Blood 2010; 116(14):2559-69.
- Nolte MA, van Olffen RW, van Gisbergen KP, van Lier RA. Timing and tuning of CD27-CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology. Immunol Rev 2009; 229(1):216-31. Review.
- Nolte MA, Arens R, van Os R, van Oosterwijk M, Hooibrink B, van Lier RA, van Oers MH. Immune activation modulates hematopoiesis through interactions between CD27 and CD70. Nat Immunol 2005; 6(4):412-8.