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The lymphatics transport material from peripheral tissues to lymph nodes, where immune responses are formed, before being transported into systemic circulation. With key roles in transport and fluid homeostasis, lymphatic dysregulation is linked to diseases, including lymphedema. Fluid within the interstitium passes into initial lymphatic vessels where a valve system prevents fluid backflow. Additionally, lymphatic endothelial cells produce key chemokines, such as CCL21, that direct the migration of dendritic cells and lymphocytes. As a result, lymphatics are an attractive delivery route for transporting immune modulatory treatments to lymph nodes where immunotherapies are potentiated in addition to being an alternative method of reaching systemic circulation. In this review, we discuss the physiology of lymphatic vessels and mechanisms used in the transport of materials from peripheral tissues to lymph nodes. We then summarize nanomaterial-based strategies to take advantage of lymphatic transport functions for delivering therapeutics to lymph nodes or systemic circulation. We also describe opportunities for targeting lymphatic endothelial cells to modulate transport and immune functions.
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Modeling Immune Search Through the Lymphatic Network
The lymphatic system is a networked structure used by billions of immune cells, including T cells and Dendritic cells, to locate and identify invading pathogens. Dendritic cells carry pieces of pathogens to the nearest lymph node, and T cells travel through the lymphatic vessels and search within lymph nodes to find them. Here we investigate how the topology of the lymphatic network affects the time for this search to be completed. Building on prior work that maps out the human lymphatic network, we develop and extend a method to infer the lymphatic network topology of mice. We compare search times for the modeled and observed topologies and show that they are similar to each other and consistent with observed immune response times. This is relevant for translating immune response times in mice, where most experimental work occurs, into expected immune response times in humans. Our analysis predicts that for large systemic infections, the topology of the lymphatic network allows immune response times to remain fast even as animal mass increases by orders of magnitude. This work advances our understanding of how the structure of the lymphatic network supports the swarm intelligence of the immune system. It also elucidates general principles relating swarm size and organization to search speed.
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- Award ID(s):
- 2020247
- PAR ID:
- 10409729
- Date Published:
- Journal Name:
- International Conference on Swarm Intelligence
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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