About the SFB 1054
Control and Plasticity of Cell-Fate Decisions in the Immune System
Immune cells, and T cells in particular, display an enormous degree of developmental plasticity, which manifests itself in the existence of multiple functional subsets, each displaying characteristic effector functions, cytokine profiles and tissue specificities. On the one hand, the segregation of the αβ T cell compartment into distinct ‘lineages’ (e.g. helper cells, killer cells, regulatory T cells, iNKT cells) is imprinted through homeostatic developmental programs. On the other hand, the encounter of invading pathogens, but also many other perturbations of immune homeostasis such as chronic infection, neoplasia or environmental changes, can elicit adaptive differentiation programs in ‘mature’ T cells that result in the acquisition of distinct functional characteristics. Since the discovery of the classical Th1/Th2 paradigm, and more recently sparked by highly sophisticated methodology for phenotypic, transcriptional and epigenetic profiling of complex cell populations at the single cell level, it has become increasingly clear that many of these apparently distinct T cell ‘subsets’ represent a continuum of flexible states with a varying degree of overlapping characteristics. Moreover, there is ample evidence that the effector phase in a T cell’s life is not necessarily a manifestation of terminal differentiation; instead, armed effectors oftentimes retain a substantial degree of plasticity, allowing them to acquire ‘novel’ functions that are tailored to subsequent immune challenges and/or changing conditions, and this may likewise apply to innate immune cells such as NK cells. Against this background, the CRC 1054 has set out to explore the determinants of this remarkable plasticity of cell-fate decisions in the immune system, both in terms of the developmental decisions of precursor cells under homeostatic conditions and in terms of the flexible and often reversible adaptation of ‘mature’ cells to immune challenges. Elucidating the signals that control immune cell-fate decisions and how these signals are read and interpreted provides fundamental insights into the biology of the immune system. At the same time, our approach is of highest relevance for translational medicine, as it reveals novel perspectives for targeted immune therapies.