Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

The centuries long pursuit to map the human lymphatic system

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

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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

References

  1. Natale, G. et al. J. Anat. 231, 417–429 (2017).

    Article  Google Scholar 

  2. Oliver, G. et al. Cell 182, 270–296 (2020).

    Article  CAS  Google Scholar 

  3. Sappey, M. P. C. (Adrien Delahaye, 1874).

  4. Stouthandel, M. E. J. et al. Anat. Rec. 302, 1681–1695 (2019).

    Article  Google Scholar 

  5. Grant, S. M. et al. J. Cell Sci. 133, jcs241828 (2020).

    Article  CAS  Google Scholar 

  6. Germain, R. N. et al. Immunol. Rev. 306, 8–24 (2022).

    Article  CAS  Google Scholar 

  7. Radtke, A. J. et al. Nat. Protoc. 17, 378–401 (2022).

    Article  CAS  Google Scholar 

  8. Takeda, A. et al. Immunity 51, 561–572.e565 (2019).

    Article  CAS  Google Scholar 

  9. Börner, K. et al. Nat. Cell Biol. 23, 1117–1128 (2021).

    Article  Google Scholar 

  10. Rockson, S. G. Circ. Res. 128, 2003–2016 (2021).

    Article  CAS  Google Scholar 

Download references

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).

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jessica M. Lukacs
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nancy E. Praskievicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Selen C. Muratoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ilsa I. Rovira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zorina S. Galis
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.J.R., J.M.L., N.E.P., S.C.M., I.I.R. and Z.S.G. conceived and wrote the manuscript.

Corresponding authors

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

Ethics declarations

Competing interests

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41591-022-01865-5

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing