Here we will study how the sensory input, local context and metabolic information are all integrated and processed into distinct outcomes in myeloid antigen presenting cells (APC). On the functional level, we will address how integration of PAMP or DAMP sensing via TLRs by DCs impacts on ‘signal 1’ (antigen presentation on MHC) and on ‘signal 2’ (costimulation presented by DCs to T cells). Furthermore we will focus on DC-derived chemokines (termed ‘signal 0’) that act before ‘signals 1’ and ‘2’. On the subcellular level we will elucidate the transcriptional, epigenomic and miRNA-based regulation of signal integration in APCs with the aim of identifying transcriptional switches. Specifically we will study how signals derived from adhesion pathways (research area B) and metabolic pathways (research area C) modify transcriptional regulation downstream of TLRs.
1. Regulation of antigen presentation (signal 1) by immune sensory input.
2. Regulation of dendritic cell-derived chemokines (signal 0) by immune sensing receptors.
3. Integration of immune and metabolic sensing in APCs.
4. Integration of integrin activation and immune sensing in APCs.