Anastasia-Olga Gkountidi

Bio: Anastasia-Olga Gkountidi is an academic researcher from ETH Zurich. The author has contributed to research in topics: Lymphatic system & Lymph. The author has co-authored 1 publications.

Imaging leukocyte migration through afferent lymphatics.

Abstract: Afferent lymphatics mediate the transport of antigen and leukocytes, especially of dendritic cells (DCs) and T cells, from peripheral tissues to draining lymph nodes (dLNs). As such they play important roles in the induction and regulation of adaptive immunity. Over the past 15 years, great advances in our understanding of leukocyte trafficking through afferent lymphatics have been made through time-lapse imaging studies performed in tissue explants and in vivo, allowing to visualize this process with cellular resolution. Intravital imaging has revealed that intralymphatic leukocytes continue to actively migrate once they have entered into lymphatic capillaries, as a consequence of the low flow conditions present in this compartment. In fact, leukocytes spend considerable time migrating, patrolling and interacting with the lymphatic endothelium or with other intralymphatic leukocytes within lymphatic capillaries. Cells typically only start to detach once they arrive in downstream-located collecting vessels, where vessel contractions contribute to enhanced lymph flow. In this review, we will introduce the biology of afferent lymphatic vessels and report on the presumed significance of DC and T cell migration via this route. We will specifically highlight how time-lapse imaging has contributed to the current model of lymphatic trafficking and the emerging notion that - besides transport - lymphatic capillaries exert additional roles in immune modulation.

CCR7-guided neutrophil redirection to skin-draining lymph nodes regulates cutaneous inflammation and infection

Abstract: Neutrophils are the first nonresident effector immune cells that migrate to a site of infection or inflammation; however, improper control of neutrophil responses can cause considerable tissue damage. Here, we found that neutrophil responses in inflamed or infected skin were regulated by CCR7-dependent migration and phagocytosis of neutrophils in draining lymph nodes (dLNs). In mouse models of Toll-like receptor–induced skin inflammation and cutaneous Staphylococcus aureus infection, neutrophils migrated from the skin to the dLNs via lymphatic vessels in a CCR7-mediated manner. In the dLNs, these neutrophils were phagocytosed by lymph node–resident type 1 and type 2 conventional dendritic cells. CCR7 up-regulation on neutrophils was a conserved mechanism across different tissues and was induced by a broad range of microbial stimuli. In the context of cutaneous immune responses, disruption of CCR7 interactions by selective CCR7 deficiency of neutrophils resulted in increased antistaphylococcal immunity and aggravated skin inflammation. Thus, neutrophil homing to and clearance in skin-dLNs affects cutaneous immunity versus pathology. Description CCR7-mediated clearance of skin-homing neutrophils in draining lymph nodes affects antibacterial immunity and inflammation in skin. Draining lymph node neutrophils regulate inflammation Neutrophil recruitment to the draining lymph node is a crucial step in various skin-related immune responses; however, the mechanism by which this occurs is unclear. Here, Özcan et al. used various skin inflammation and infection models to track the movement of neutrophils homing to and leaving the skin. They found that the skin neutrophils migrated to the skin-draining lymph nodes in a CCR7-mediated manner. In the draining lymph node, neutrophils were cleared by phagocytosis by conventional dendritic cells. These CCR7-driven neutrophils were crucial for protection against bacterial infection and TLR7 ligand–induced inflammation. Together, the migration of neutrophils from the skin to the draining lymph node, and their subsequent clearance, is important for skin immune responses.