Description of the Research

Our research aims to understand how immune cells – and especially dendritic cells – navigate and move according to different molecular cues in changing tissue environment.

Gradients of extracellular signaling molecules are a fundamental concept in biology, and gradients of chemotactic cytokines, and chemokines, position cells in development, malignancy, and immunity. Chemotaxis, including gradient sensing and directional migration according to it, is especially critical for leukocytes such as the antigen-presenting dendritic cells (DCs), which need to be recruited within short time frames and to migrate directionally over long distances. Efficient, directional DC migration is crucial for a functioning immune system, and defects in DC navigation can lead to various autoimmune disorders. The same guidance clues have been shown to be utilized also by certain metastasizing cancers. Nevertheless, how chemokine gradients are regulated and maintained in vivo to ensure efficient leukocyte migration in changing conditions has remained somewhat of a mystery.

Our recent work with Prof. Michael Sixt revealed soluble self-generated chemokine gradients as novel regulators of leukocyte migration: by constant depletion of a soluble chemokine, DCs were able to guide not just themselves, but also the co-migrating T cells irrespective of the shape of the pre-existing gradient (Alanko et al. 2023). Moreover, these self-generated gradients gave the cells the ability to navigate in complex environments and sense upcoming obstacles from a distance, thereby ensures efficient directed cell migration in changing conditions. This work was the first indication of self-generated gradients regulating immune cells, and as such, has opened up a completely new and unexplored area of research, which we are further investigating in our ongoing research. In addition, the role of the local tissue environment on DC navigation and the subsequent adaptive immune response is investigated with techniques including various in vitro cell migration setups, advanced matrix biology, and quantitative live cell microscopy.

Together, our research aims to define new targets and methodology for future development of advanced immunomodulating therapies, and to answer the very basic, yet, fundamental question in biology: how do our immune cells know where to go?

Funding

Our research is funded by Research Council of Finland and Instrumentarium Science Foundation.