Intercellular Cytokine Communication Networks in the Immune System: The cytokine language
The immune system functions by a coordinated response of many cell types that exchange information via a complex communication network. Important mediators of that intercellular communication are cytokines - small proteins that are secreted and can be detected by cells of the immune system, as well as by cells of other tissues.
The cytokine interaction network forms a (molecular) language by which immune cells communicate, to coordinate a desired immune response.
The motivation for our research is to obtain a better quantitative understanding of this intercellular communication network. We use a modular approach, characterizing the function of simple network modules that will provide the basic building blocks of the network. Studies at the level of single cells can avoid ambiguities that arise due to heterogeneous responses in cell populations, and provide quantitative data under well-defined conditions, which is necessary for mathematical modeling. We aim to combine experimental studies and mathematical modeling to gain new insights on the function of these networks.
We are developing and applying advanced fluorescent microscopy and microfluidics systems to enable studies of single living cells in well defined environments and under controlled interactions.
Currently, we focus on network modules involved in T-cell activation and differentiation. Some questions of interest include - How does autoregulation effect thresholds for cell activation? What are the rules for combinatorial signaling, when a cell responds simultaneously to a number of cytokines? What roles are played by stochasticity in differentiation processes? Another area of interest is the study of intercellular interactions in tumor microenvironments and their role in tumor development.