Leibniz MMS Days 2019 - Abstract
Thurley, Kevin
Mammalian immune responses are tightly controlled. Decisions on the strength and type of an immune response are made by the collaborative action of a diverse set of immune cells, such as T cells and antigen-presenting cells, interacting by diffusible mediators, the cytokines. Complex disease conditions are related to immune cell communication, including rheumatoid arthritis and cancer, but many aspects of immune cell communication remain poorly understood. For example: What is the spatial range of cytokine signals under physiological conditions, and how is it controlled? Does collective decision-making have fundamental advantages with respect to intracellular decision-making alone? Can we identify design principles of cell-to-cell communication networks, in analogy to intracellular signaling networks? Focusing on the well-characterized T-cell cytokine interleukin-2, we performed extensive 3D simulations and elucidated how cytokine secretion and competitive uptake determine the signaling range. For the analysis of more general cell-cell communication networks, we developed a framework based on measurable cellular input-to-output characteristics, and found conditions that generate biphasic responses or control synchronization and delay of cell-population responses.
Literature:
Thurley K, Altschuler SJ, Wu LF, Cell Systems 6:355 (2018).
Thurley, Gerecht, Friedmann, Höfer, PLoSComp Biol (2015).