On their health missions, they have to get from A to B as effectively as possible. In addition, immune cells apparently show each other their way to the goal, according to a study. Basically, they are guided by signal substances that emanate from the target. By absorbing these molecules, however, they then increase the gradient of clue substances in their environment and thus increase the directional effect. This new insight into the mechanisms of the immune system could also have medical significance, the researchers say.
Malignant microbes, toxins, cancer cells...: If our immune system didn't constantly keep harmful actors in check, all hell would break loose in the body. The amazing effectiveness of the "body police" is based on fascinating concepts that have been the subject of research for a long time. An important aspect is the complex coordination of the movements of the different units of the immune cells in the body. However, there are still numerous unanswered questions about how they orientate themselves during their missions and migrate purposefully through the body tissues.
The focus of the study by researchers led by Jonna Alanko from the Institute of Science and Technology Austria (ISTA) in Klosterneuburg was a special body police unit: the so-called dendritic cells act as mediators between the first reaction to intruders - the innate immune response - and the adaptive immune response: a delayed response that targets specific germs and creates memories to ward off future infections. For this task, the dendritic cells patrol the body's tissues and become active when they have discovered a potential source of disease: to "report" it, they then migrate to the nearest lymphatic tissue, where they convey a kind of battle plan for the further development of the immune reaction.
Not just passive “sniffing out” the path
In principle, it already seemed clear that the dendritic cells find their way using signal proteins that emanate from the lymph nodes. Until now, it was assumed that they simply follow the gradient of these so-called chemokines - they move towards the area with the higher concentration. The immune cells have a “nose” for this groundbreaking signaling molecule: the receptor “CCR7” sits on their surfaces and reacts to the chemokine. The scientists have now looked more closely at this system as part of their study. They examined the processes using molecular biological methods and labeling of the relevant molecules.
"We have now been able to show that the CCR7 receptor not only perceives the chemokine, but also actively contributes to shaping the distribution of its concentrations," says Alanko. With the help of their detection techniques, the researchers were able to document how dendritic cells actively incorporate chemokines via the CCR7 receptor during their migration. As the team explains, this leads to a local reduction in chemokine concentration. This can then increase the groundbreaking effect: the contrast becomes clearer and the cell can move more effectively towards the target.
Possibly far-reaching significance
To further elucidate the mechanism's importance for cell movement and dynamics, the scientists also performed computer simulations based on the information obtained. As they report, the results reflect the fact that the effect can not only serve as a guide for individual cells. Together, many of the immune cells apparently create a kind of large signpost: "The more cells there are, the stronger the gradient they create. It shows a collective nature of this phenomenon,” says co-author Can Ucar from ISTA.
They also found the first indications that the concept also plays a role in the movement of other immune cells: Accordingly, the orientation of T cells - immune cells that destroy harmful germs - could also be shaped by this self-generated gradient concept. Contrary to what was previously assumed, immune cells could not only react passively to chemokines, but also play a much more active role by picking up the signals and thus shaping their environment. This could affect their own movement as well as that of other immune cells in an important way. "Hopefully, the research projects that are now underway will give us more information about this novel principle of interaction between cell populations," says Ucar.
Ultimately, the discovery could also have medical potential, say the scientists: New starting points could become apparent that might make it possible to better direct immune cells to specific locations, such as to tumors or foci of infection.
Source: Institute of Science and Technology Austria, specialist article: Science Immunology, doi: 10.1126/sciimmunol.adc9584