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The centuries long pursuit to map the human lymphatic system

Nature Medicine volume 28, pages 1518–1520 (2022)Cite this article

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Owing to its expansive yet enigmatic nature, the lymphatic system remains one of the last frontiers of anatomical medicine. Over the past few years, multidisciplinary efforts to construct a contemporary map have been championed by ourselves and others4. To encourage exploration and solicit domain expertise, a recent workshop organized by the National Institutes of Health (NIH) in collaboration with the Boston Lymphatic Symposium, highlighted remaining challenges in the field. These obstacles include the body-wide reach and scale of the lymphatic system, which is distributed within and throughout several tissues and organ systems. Furthermore, lymphatic vessels are imperceptible to the human eye owing to their small size and cargo, a clear protein-rich fluid known as lymph4. These characteristics, and probably others, have preserved the mystique of the lymphatic system while contributing to the scarcity of medical imaging and other diagnostic methods needed for research and clinical management.

Beyond connecting hundreds of lymphoid organs, lymphatic vessels transport tissue metabolites and peripheral antigens through capillaries lined by specialized lymphatic endothelial cells2. Malfunctions of lymphatic vessels, arising from inborn mutations or cancer treatment10, contribute to serious medical conditions such as lymphedema. Therefore, an integrated portrait of the human lymphatic system is needed to prevent, diagnose, and treat lymphedema and other related conditions, estimated to affect 1 in 1,000 Americans and 250 million patients worldwide. To this end, we envision that the application of clinical imaging approaches10, in combination with single-cell proteomic and transcriptomic technologies, will yield insights into anatomical variants and genetic biomarkers associated with increased risk for lymphedema.

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Fig. 1: Marie Sappey and Henri Rouvière described the lymphatic system.
Fig. 2: Modern imaging techniques in lymphatic research.

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Acknowledgements

This work was supported by the Intramural Research Program of the NIH, NIAID and NCI, and the Extramural Programs at NIH and NHLBI. We are very appreciative of insights and resources provided by R. N. Germain and image provided by C. Chu. We are grateful for domain expertise from our colleagues: D. Singhal, M. Amore, K. Börner, E. Chaikof, M. Detmar, M. Hollmén, J. Iliff, M. Itkin, T. Makinen, G. Oliver, T. Padera, E. Quardokus, H. Suami and G. Weber. We are indebted to D. M. Sullivan and A. Yarmosh who conceived and executed Fig. 1. The confocal and IBEX images in Fig. 2 were obtained experimentally by A. J. Radtke and C. Chu (human jejunum).

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Authors and Affiliations

  1. Lymphocyte Biology Section and Center for Advanced Tissue Imaging, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA

    Andrea J. Radtke

  2. Division of Scientific Categorization and Analysis, Office of Research Reporting and Analysis, Office of Extramural Research, Office of the Director, National Institutes of Health, Bethesda, MD, USA

    Jessica M. Lukacs & Nancy E. Praskievicz

  3. Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Selen C. Muratoglu, Ilsa I. Rovira & Zorina S. Galis

Authors
  1. Andrea J. Radtke
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  2. Jessica M. Lukacs
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  4. Selen C. Muratoglu
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A.J.R., J.M.L., N.E.P., S.C.M., I.I.R. and Z.S.G. conceived and wrote the manuscript.

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Correspondence to Andrea J. Radtke or Zorina S. Galis.

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All the authors are government employees. The authors do not have any financial conflict of interests. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Institutes of Health or any of its Institutes; or the US Department of Health and Human Services.

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Radtke, A.J., Lukacs, J.M., Praskievicz, N.E. et al. The centuries long pursuit to map the human lymphatic system. Nat Med 28, 1518–1520 (2022). https://doi.org/10.1038/s41591-022-01865-5

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