Signpost for sentinel cells

February 16, 2016 by Fabio Bergamin, ETH Zurich
Signpost for sentinel cells
Dendritic cells (green) are migrating actively within lymphatic capillaries (red; microscopic image). Credit: ETH Zurich / Erica Russo

Sentinel cells of the immune system can enter the finest lymphatic capillary vessels present in tissues. Researchers at ETH Zurich have now discovered the molecular signpost that guides these cells in the direction of the nearest lymph node.

Lymphatic vessels can be considered the pneumatic tubes of our immune system; the its control centres. Antibodies and , which are able to fight against pathogens invading our bodies, mature in these centres. It is through that information about these pathogens reaches the lymph nodes. An armada of sentinel , called dendritic cells, are decentrally positioned in tissues to take up pathogens. After uptake of the pathogen, the dendritic cells move into the lymphatic vessels and eventually trigger an alarm in the draining lymph node.

In larger lymphatic vessels, dendritic cells are passively transported by lymph flow. However, in the initial capillary vessels of the lymphatic vessel tree, where dendritic cells begin their migration, this is not the case. Here, lymph flow is too weak. Immunologists at ETH Zurich have now discovered how dendritic cells advance from the capillary vessels towards the lymph node. Lymphatic flow is still involved in this process, but only indirectly.

A few years ago, Cornelia Halin, professor at the Institute of Pharmaceutical Sciences, and her team observed that dendritic cells migrate in a zigzag pattern within lymphatic capillaries (see medicalxpress.com/news/2012-08 … mphatic-vessels.html ). It is an active but rather inefficient, forward movement; Halin speaks of '"patrolling".

Dendritic cells (green) patrol within lymphatic capillaries (red). Credit: Russo et al. Cell Reports 2016

Molecular mediator with density gradient

But how do dendritic cells find the direction of the nearest lymph node? Erica Russo, a doctoral student in Halin's group, has succeeded in showing, in mice, that the cells orient themselves in the capillaries with the help of a molecular mediator named CCL21. "The inside of the capillary wall is lined with CCL21 molecules which increase in density in the direction of lymph nodes," explains Russo. Since dendritic cells have a receptor for CCL21, they manage to sense the direction - by "smelling" the higher concentration of the mediator.

Using, inter alia, cell culture experiments, the scientists were also able to determine why the concentration of the CCL21 signpost molecules increases in the direction of the lymph nodes. "The extremely weak flow in lymphatic capillaries is not strong enough to carry the cells along, however it is sufficient to move the CCL21 signpost molecules, which weakly interact with the vessel wall, in the direction of lymph nodes. This establishes a directional gradient, which the cells follow," says Russo.

For the time being, it is still unclear why do not move directly through lymphatic capillaries, but instead follow a zigzag course. One hypothesis, which Halin would like to further investigate, is whether the cells exchange information with the vessel walls or with other present within the vessel. This could potentially impact their function as immune sentinels.

Explore further: Preschool within lymphatic vessels

More information: Erica Russo et al. Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels, Cell Reports (2016). DOI: 10.1016/j.celrep.2016.01.048

Related Stories

Preschool within lymphatic vessels

August 9, 2012
Not only infants crawl. ETH researchers have shown that so-called dendritic cells, important cells of the immune system, use a similar mode of movement more often than previously assumed. The scientists used intravital microscopy ...

Impact of Type 2 diabetes on lymphatic vessels identified

July 14, 2015
Approximately 28 million Americans live with Type 2 diabetes, a condition characterized by high blood sugar levels. Until now, the disease's effect on the body's lymphatic vessels has been unknown. A study by University of ...

How cancer tricks the lymphatic system into spreading tumors

May 11, 2015
Swollen lymph nodes are often the earliest sign of metastatic spread of cancer cells. Now cancer researchers and immunologists at Sweden's Karolinska Institutet have discovered how cancer cells can infiltrate the lymphatic ...

Sieve-like structure regulates the transport of proteins and migration of white blood cells into lymph nodes

February 11, 2015
Researchers have uncovered a sieve-like structure in lymph nodes that regulates the transport of proteins and migration of white blood cells into lymph nodes. The discovery, made by scientists working at the University of ...

Evidence strengthens link between NSAIDs and reduced cancer metastasis

February 13, 2012
A new study reveals key factors that promote the spread of cancer to lymph nodes and provides a mechanism that explains how a common over-the-counter anti-inflammatory medication can reduce the spread of tumor cells through ...

Researchers develop 'killer cells' to destroy cancer in lymph nodes

November 12, 2015
Cornell biomedical engineers have developed specialized white blood cells - dubbed "super natural killer cells" - that seek out cancer cells in lymph nodes with only one purpose: destroy them. This breakthrough halts the ...

Recommended for you

Scientists produce human intestinal lining that re-creates living tissue inside organ-chip

February 16, 2018
Investigators have demonstrated how cells of a human intestinal lining created outside an individual's body mirror living tissue when placed inside microengineered Intestine-Chips, opening the door to personalized testing ...

Researcher explains how statistics, neuroscience improve anesthesiology

February 16, 2018
It's intuitive that anesthesia operates in the brain, but the standard protocol among anesthesiologists when monitoring and dosing patients during surgery is to rely on indirect signs of arousal like movement, and changes ...

Data wave hits health care

February 16, 2018
Technology used by Facebook, Google and Amazon to turn spoken language into text, recognize faces and target advertising could help doctors fight one of the deadliest infections in American hospitals.

Team reports progress in pursuit of sickle cell cure

February 16, 2018
Scientists have successfully used gene editing to repair 20 to 40 percent of stem and progenitor cells taken from the peripheral blood of patients with sickle cell disease, according to Rice University bioengineer Gang Bao.

Appetite-controlling molecule could prevent 'rebound' weight gain after dieting

February 15, 2018
Scientists have revealed how mice control their appetite when under stress such as cold temperatures and starvation, according to a new study by Monash University and St Vincent's Institute in Melbourne. The results shed ...

First study of radiation exposure in human gut Organ Chip device offers hope for better radioprotective drugs

February 14, 2018
Chernobyl. Three Mile Island. Fukushima. Accidents at nuclear power plants can potentially cause massive destruction and expose workers and civilians to dangerous levels of radiation that lead to cancerous genetic mutations ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.