Guidance factors orchestrating regulatory T cell positioning in tissues during development, homeostasis, and response

Over their lifetime, regulatory T cells (Treg) recalibrate their expression of trafficking receptors multiple times as they progress through development, respond to immune challenges, or adapt to the requirements of functioning in various non-lymphoid tissue environments. These trafficking receptors, which include chemokine receptors and other G-protein coupled receptors, integrins, as well as selectins and their ligands, enable Treg not only to enter appropriate tissues from the bloodstream via post-capillary venules, but also to navigate these tissues to locally execute their immune-regulatory functions, and finally to seek out the right antigen-presenting cells and interact with these, in part in order to receive the signals that sustain their survival, proliferation, and functional activity, in part in order to execute their immuno-regulatory function by altering antigen presenting cell function. Here, we will review our current knowledge of when and in what ways Treg alter their trafficking properties. We will focus on the chemokine system and try to identify specialized, non-redundant roles of individual receptors as well as similarities and differences to the conventional T cell compartment.