The territory of the immune cells. The picture shows a special image of skin tissue: blood vessels (red), lymphoid tissue (green) and the signal chemokine CCL21 (blue) Credit: Image courtesy of Michele Weber and Michael Sixt
Reading aloud You wander through a confusing area: in search of pathogens, the immune cells leave the bloodstream and patrol through the tissues and organs. Then they return to the bloodstream via the lymphatic vessels to go on a criminal chase elsewhere. But how do you find your way back to the lymphatic vessels? A recent study shows for the first time experimentally that immune cells are based on the concentration gradient of signaling substances - they sniff or feel the way. Researchers have long suspected that immune cells can detect the chemical composition of their environment either by "touching" structural molecules or by "smelling" signal molecules in a soluble form - as had been suggested by studies on cell cultures. The orientation according to the olfactory principle could work in a similar way as the search for a flower in a dark room - the scent points the way. As the smell grows closer to the source, the immune cell orients itself at the concentration gradient of a dissolved signaling molecule, so the assumption. Now, researchers led by Michael Sixt from the Austrian Institute of Science and Technology have been able to show for the first time in mouse skin tissue how immune cells move purposefully through complex tissue.

Where is the lymphatic vessel going?

The results suggest that the immune cells actually use a combination of touch and smell when patrolling the skin tissue. They follow the concentration gradient of signal molecules, which are not soluble, but are bound to sugar molecules in the connective tissue. When the researchers labeled the immune cells and the signal substance chemokine CCL21, they observed that the chemokine emanates exclusively from lymphatic vessels. It spreads in the surrounding tissue and thus forms a concentration gradient. However, it does not remain mobile like an odorant, but anchors itself permanently to sugar molecules.

Researchers tracked the system by mapping maps of the chemokine distribution and comparing them to the cell's migration routes. As it turns out, the immune cells find their way to the next lymphatic vessel by sensing the concentration of chemokine on their surface and then moving toward the higher concentration. To test this, the researchers "flooded" the test tissue with chemokine. The result confirmed the assumption that the immune cells wandered around - they were no longer able to find the lymphatic vessel. display

The fact that the signal molecules are not soluble, but bound to connective tissue molecules, has a convincing reason: If the groundbreaking substance were soluble, pressure on the tissue would cause fluid turbulence that would destroy the gradient. An anchored lead structure, on the other hand, is insensitive.

According to the researchers, the results could provide important information for the development of therapies and medicines. Michael Sixt emphasizes: "It is important to understand how immune cells move and orient themselves. Only then can we reasonably think about strategies to influence their behavior. "

Michael Sixt (Institute of Science and Technology) et al .: Science, 10.1126 / science.1228456 © - Martin Vieweg


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