In this area we address the significance of incoming signals in the local context. We focus on signals that are either driven by immune sensing receptors or that impact on the sensitivity or the qualitative and quantitative outcome of immune sensing receptor signaling. One important focus is the regulation of cell motility and adhesion by chemokines and integrins, which are prerequisites for effective immune sensor functions and can also directly regulate immune sensor signaling. To this end, we will explore the signal transduction pathways initiated by the inflammatory chemokine CCL17, which is responsible for the coordinated regulation of tissue-specific and inducible immune cell motility. In addition, beta-2 integrins, which are known for their signaling cross-talk with growth factor receptors, can also modulate sensory receptor signaling, e.g. TLR4. We will systematically investigate the impact of integrin signaling on key sensory receptors, such as TLR2 and NLRP3 in vitro and also functionally analyze gene targeted mice with conditional and inducible systems in vivo. The second major area of interest in this section is the role of organ-specific immune cells and selected non-immune cells in immune sensing. We will employ the concerted knowledge and available experimental systems of this Cluster for three model organs (CNS, liver, skin). In particular, we will investigate the role of immune inhibitory receptors of the brain on immune sensing, the reverse role of T cell co-stimulators/inhibitors on the local immune sensing functions of tissue-specific antigen presenting cells and the control of skin-associated immune responses by the aryl hydrocarbon receptor (AhR), a sensor of environmental low molecular weight chemicals.
1. Immune sensory signaling in myeloid cell chemotaxis.
2. Impact of integrins on immune sensing receptor function
3. Immune sensing in tissue-resident immune cells
4. Regulation of local immune sensing in organ-resident non-immune cells.