Abstract
The lymphatics fulfill a vital physiological function as the conduits through which leucocytes traffic between the tissues and draining lymph nodes for the initiation and modulation of immune responses. However, until recently many of the molecular mechanisms controlling such migration have been unclear. As a result of careful research, it is now apparent that the process is regulated at multiple stages from initial leucocyte entry and intraluminal crawling in peripheral tissue lymphatics, through to leucocyte exit in draining lymph nodes where the migrating cells either participate in immune responses or return to the circulation via efferent lymph. Furthermore, it is increasingly evident that most if not all leucocyte populations migrate in lymph and that such migration is not only important for immune modulation, but also for the timely repair and resolution of tissue inflammation. In this article, I review the latest research findings in these areas, arising from new insights into the distinctive ultrastructure of lymphatic capillaries and lymph node sinuses. Accordingly, I highlight the emerging importance of the leucocyte glycocalyx and its novel interactions with the endothelial receptor LYVE-1, the intricacies of endothelial chemokine secretion and sequestration that direct leucocyte trafficking and the significance of the process for normal immune function and pathology.
Highlights
The lymphatics form an extensive network that facilitates the drainage of plasma leaked from the peripheral vasculature and its re-uptake by the venous circulation for maintenance of fluid homeostasis [1, 2]
In the case of dendritic cells (DCs), this has revealed an intricate and closely co-ordinated mechanism in which physical contact of migrating leucocytes with lymphatic endothelium triggers the local exocytosis of CCL21 and formation of LYVE-1+ transmigratory cups which envelop the migrating cells and promote their transit into the vessel lumen
Parallel observations that transmigrating T cells and macrophages elicit the formation of similar endothelial protrusions containing ICAM-1, VCAM-1 and/or LYVE-1, and reliance on an HA glycocalyx or β2 integrin adhesion, raise the possibility that lymph-migrating leucocytes exploit a common mechanism for vessel entry [76, 85, 101]
Summary
The lymphatics form an extensive network that facilitates the drainage of plasma leaked from the peripheral vasculature and its re-uptake by the venous circulation for maintenance of fluid homeostasis [1, 2]. Research using new techniques and animal models for tracking and imaging cell migration, combined with the efforts of a wide interdisciplinary community of interested scientists, has led to huge advances in our understanding of leucocyte trafficking in the lymphatic system and its immune significance.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
