The CRC 1054 explores plasticity of cell-fate decisions in the immune system in order to identify differentiation signals that confer stability and flexibility and to characterize the molecular basis for how these signals are read by T cells. The CRC 1054 therefore aims to obtain a comprehensive understanding of the relationship between extracellular and intracellular signals and T cell differentiation. In the second funding period the common goal of our multidisciplinary consortium is to analyse in depth how distinct types of T cells differentiate into their prospective effector cell subsets, when exposed to clearly defined signals provided by the tissue microenvironment or by other immune cell types such as NKT cells and dendritic cell subpopulations. We will focus our research efforts on studying the differentiation of Th1, Th2, Th17, nTreg, iTreg, Tfh cells, activated effector T cells and exhausted T cells to get a better understanding how these T cell subsets and functional states are related. Furthermore, differentiation and functional specialisation of dendritic cell subpopulations, which shape T cell differentiation, will be investigated. Using viral infections, patient cohorts of vaccinees and disease models for multiple sclerosis, inflammatory bowel disease and diabetes we will analyse immune cell differentiation during pathogen challenges or autoimmune diseases. Ultimately, we aim to identify molecules and cells types, which can be targeted to manipulate immune cell differentiation in order to prevent or revert pathology in autoimmune, inflammatory and infectious diseases.