Newly discovered cell type interplays with immune cells in vascular disease

2023-01-23

Researchers at IGP have discovered a new cell subtype in the lymphatic vessels that interacts with immune cells in lymphatic malformations. This newly discovered interplay between the immune system and the lymphatic system could be used to treat diseases with lymphatic malformations.

Malformations in the body’s lymphatic vessels are chronic diseases that can result in pain, bleeding and functional impairment of nearby organs. The IGP researchers have discovered a new subtype of cells in lymphatic vessels that regulate the excess vessel growth causing the vessel malformations.

The researchers name the new cells immune-interacting lymphatic endothelial cells, iLECs. They are sitting at the ends of lymphatic vessels in the skin and they express genes involved in the regulation of the immune response. The findings suggest that the lymphatic vasculature might play overlooked roles in normal physiology and diseases related to the immune system in peripheral organs.

“We studied a mouse model where a certain mutation caused uncontrolled vessel growth and saw that the iLEC population was expanded. In the mutant mice, iLECs also produced substances that promote recruitment of macrophages, a type of white blood cells, which in turn produce growth factors that stimulate lymphatic vessel growth,” says Milena Petkova, first author of the study.

“We are very excited about these findings as they indicate a crosstalk between iLECs and macrophages that can be therapeutically targeted to treat lymphatic malformations,” says Taija Mäkinen, who led this study.

Indeed, the researches show that depletion of the macrophages, or blocking their recruitment or function, led to reduced pathological growth of lymphatic malformation in the mouse model. Cells with molecular characteristics similar to iLECs were also found in tissue samples from patients with lymphatic malformations.

It is increasingly recognised that the lymphatic vasculature is a highly multifaceted organ system that performs important functions in the different tissues they occupy, far beyond simply transporting fluid and immune cells. The authors believe that uncovering these biological functions, such as its interaction with the immune system as described here, may eventually lead to the insight that pathologies such as cancer and autoimmune diseases could be treated by targeting the lymphatic vessels.

The study is published in Journal of Experimental Medicine.

More information:

Article in Journal of Experimental Medicine

Taija Mäkinen’s research

Microscope image of lymphatic vessels and immune cells in a mouse model
Visualisation of lymphatic vessels (red) and immune cells (cyan) in a mouse model of lymphatic malformation. Blood vessels are shown in blue. Image: Milena Petkova.

Last modified: 2022-01-26