Signal Transduction
Marcus Thelen, Group Leader
Chemotactic cytokines and their cognate receptors are the most important regulators for cell migration in vertebrates. The chemokine system not only controls leukocyte trafficking during immune homeostasis, surveillance and responses, but also the positioning of somatic cells, e.g. during development, and in pathological situations such as tumor growth and spreading. By and large, cells migrate along guidance cues formed by gradients of appropriate chemokines. The latter are produced by various cell types, such as endothelium, epithelium and stromal cells, and are often retained at their surface. While most chemokine receptors follow a common paradigm of cell activation, more recently a small group of atypical chemokine receptors was described. Their function is to scavenge chemokines and therefore balance the activity of chemokines. For the proper resolution of an immune response, scavenging of chemokines is important to cease the recruitment of inflammatory cells and to dampen the response. During development, the atypical receptors can carve gradients and restrict the availability of chemokines for their cognate receptors, thereby controlling cell positioning.