Millions worldwide are affected by disorders of the lymphatic system—or face increased risk due to surgery, injury, or infection. Despite its essential role in immunity and overall health, the lymphatic system remains one of the least understood systems in the human body.

Our Society is committed to bridging this knowledge gap by connecting healthcare professionals, researchers, and patients, and by actively supporting lymphatic research. Scientific breakthroughs are crucial to advancing the diagnosis and treatment of lymphedema—and ultimately, to improving patients’ quality of life.

The lymphatic system is a network of vessels and organs that helps keep your body healthy. It includes lymph nodes, tonsils, the thymus, and the spleen.

Its main job is to drain extra fluid from your body’s tissues and return it to your bloodstream. This fluid, called lymph, also carries immune cells that help fight infections. Lymph flows in one direction—from the body’s tissues back to the heart—passing through lymph nodes that filter out harmful substances along the way.

Besides keeping fluid levels balanced, the lymphatic system also:

• Supports your immune system by detecting and fighting germs
• Absorbs fats from your digestive system
• Helps reduce swelling and inflammation after injury or infection

Although it works quietly in the background, the lymphatic system is essential for your overall health.

Figure 1: Microscopy image of a collecting lymphatic vessel (green) surrounded by smooth muscle cells (red).

Figure 2: Understanding the Progression of Lymphedema
The exact sequence of events that lead to the physical changes seen in lymphedema is still not fully understood. Research from both clinical cases and animal studies shows that as lymphedema develops, the skin and lymphatic vessels undergo inflammation, fat tissue changes, and scarring (fibrosis).
However, it’s still unclear when these changes occur or how they are connected. For example, scientists don’t yet know:

1. Whether fat tissue changes and inflammation happen at the same time or as separate processes

2. If fat buildup in lymphedema contributes to fibrosis—similar to what is seen in obesity

More research is needed to uncover how these processes interact and evolve over time, which may help improve treatment and prevention strategies.

While we’ve made progress in understanding lymphedema, many questions about how the disease develops remain unanswered. In the past, it was believed that lymphedema was mainly caused by a buildup of lymph fluid in the soft tissues. However, recent research suggests it’s far more complex.

We now understand that lymphedema triggers a chain reaction in the body. When lymphatic drainage is impaired, proteins and fats collect in the tissue. This leads to lasting changes—including fat buildup, inflammation, and tissue scarring (fibrosis).

These changes don’t happen in isolation. They affect different parts of the tissue and seem to progress together, but the exact timing and relationships between them are still unclear.

Our ongoing research is focused on uncovering:

• How these changes develop
• How they are connected
• When they occur during the disease

By solving these mysteries, we hope to discover new ways to prevent, diagnose, and treat lymphedema—ultimately improving care and quality of life for those affected.

Azhar SH, Lim HY, Tan B-K and Angeli V (2020) The Unresolved Pathophysiology of Lymphedema. Front. Physiol. 11:137. doi: 10.3389/fphys.2020.00137

Tay MHD, Lim SYJ, Leong YFI, Thiam CH, Tan KW, Torta FT, Narayanaswamy P, Wenk M, Angeli V. Halted Lymphocyte Egress via Efferent Lymph Contributes to Lymph Node Hypertrophy During Hypercholesterolemia. Front Immunol. 2019 Mar 27;10:575. doi: 10.3389/fimmu.2019.00575.

Wang JK, Yeo KP, Chun YY, Tan TTY, Tan NS, Angeli V, Choong C Fish scale-derived collagen patch promotes growth of blood and lymphatic vessels in vivo. Acta Biomater. 2017 Sep 6. pii: S1742-7061(17)30564-0. doi: 10.1016/j.actbio.2017.09.001.

Yeo KP, Angeli V. Bidirectional Crosstalk between Lymphatic Endothelial Cell and T Cell and Its Implications in Tumor Immunity. Front Immunol. 2017 Feb 6;8:83. doi: 10.3389/fimmu.2017.00083.

Pin YK, Khoo K, Tham M, Karwai T, Hwee TC, Puaux AL, Phua ML, Kato M, Angeli V, Abastado JP. Lymphadenectomy promotes tumor growth and cancer cell dissemination in the spontaneous RET mouse model of human uveal melanoma. Oncotarget. 2015 Dec 29;6(42):44806-18. doi: 10.18632/oncotarget.6326.

Tan KW, Chong SZ, Angeli V. Inflammatory lymphangiogenesis: cellular mediators and functional implications. Angiogenesis. 2014 Apr;17(2):373-81. doi: 10.1007/s10456-014-9419-4.

Lim HY, Thiam CH, Yeo KP, Bisoendial R, Hii CS, McGrath KC, Tan KW, Heather A, Alexander JS, Angeli V.Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-mediated transport of HDL. Cell Metab. 2013 May 7;17(5):671-84. doi: 10.1016/j.cmet.2013.04.002.

Tan KW, Yeo KP, Wong FH, Lim HY, Khoo KL, Abastado JP, Angeli V. Expansion of cortical and medullary sinuses restrains lymph node hypertrophy during prolonged inflammation.

J Immunol. 2012 Apr 15;188(8):4065-80. doi: 10.4049/jimmunol.1101854.

Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration.

Lim HY, Rutkowski JM, Helft J, Reddy ST, Swartz MA, Randolph GJ, Angeli V. Am J Pathol. 2009 Sep;175(3):1328-37. doi: 10.2353/ajpath.2009.080963

Join us in raising awareness of lymphedema among the public and across various healthcare disciplines. Your generous support enables us to expand our outreach, provide essential resources for patients, and educate communities—helping both current and future patients live better, informed lives. Every contribution makes a meaningful difference.