2023-09-03 11:15:38
When fighting disease, our immune cells need to reach their target quickly. Researchers from the Austrian Institute of Science and Technology (ISTA) have found that immune cells actively generate their own guidance system to navigate complex environments. This challenges previous notions about these movements. The researchers’ findings, published in the journal Scientific Immunology, improve our knowledge of the immune system and propose new potential approaches to improve the human immune response.
Immunological threats such as germs or toxins can appear anywhere in the human body. Fortunately, the immune system – our own protective shield – has complex ways to deal with these threats. For example, a crucial aspect of our immune response involves the coordinated collective movement of immune cells during infection and inflammation. But how do our immune cells know which direction to take?
A group of scientists from the Sixt Group and the Hannezo Group of the Austrian Institute of Science and Technology (ISTA) have looked into this question. In their study, published today in Scientific immunologyresearchers have shed light on the ability of immune cells to collectively migrate through complex environments.
Dendritic cells — The Messengers
Dendritic cells (DC) are one of the key players in our immune response. They function as a messenger between the innate response – the body’s first reaction to an invader, and the adaptive response – a delayed reaction that targets very specific germs and creates memories to fight off future infections. Like detectives, DCs scan fabrics for intruders. Once they locate an infection site, they are activated and immediately migrate to the lymph nodes, where they hand over the battle plan and initiate the next steps in the cascade. Their migration to the lymph nodes is guided by chemokines – small signaling proteins released by the lymph nodes – which establish a gradient. In the past, DCs and other immune cells were thought to respond to this external gradient, moving towards a higher concentration. However, new research at ISTA is now challenging this notion.
One receiver – two functions
Scientists took a close look at a receptor, a surface structure found on activated DCs, called ‘CCR7’. The essential function of CCR7 is to bind to a specific molecule in the lymph nodes (CCL19), which triggers the next steps in the immune response. “We found that CCR7 not only detects CCL19, but also actively helps shape the distribution of chemokine concentrations,” says Jonna Alanko, a former postdoc in Michael Sixt’s lab.
Using different experimental techniques, they demonstrated that as DCs migrate, they take up and internalize chemokines via the CCR7 receptor, resulting in a local decrease in chemokine concentration. With fewer signaling molecules, they move to higher concentrations of chemokines. This dual function allows immune cells to generate their own guidance signals to more effectively orchestrate their collective migration.
Movement depends on cell population
To quantitatively understand this mechanism at the multicellular scale, Alanko and his colleagues teamed up with theoretical physicists Edouard Hannezo and Mehmet Can Ucar, also at ISTA. Using their expertise in movement and cellular dynamics, they established computer simulations capable of replicating Alanko’s experiments. Using these simulations, the scientists predicted that the movement of dendritic cells depends not only on their individual responses to the chemokine but also on the density of the cell population. “This was a simple but non-trivial prediction: the more cells there are, the sharper the gradient they generate – this really highlights the collective nature of this phenomenon!” said Can Ucar.
Additionally, the researchers found that T-lymphocytes – specific immune cells that destroy harmful germs – also benefit from this dynamic interaction to enhance their own directional movement. “We look forward to learning more about this new principle of interaction between cell populations with ongoing projects,” continues the physicist.
Improve immune response
These findings are a step in a new direction in how cells move inside our bodies. Contrary to what was previously believed, immune cells not only respond to chemokines, but also play an active role in shaping their own environment by consuming these chemical signals. This dynamic regulation of signaling signals provides an elegant strategy to guide their own movement and that of other immune cells.
This research has significant implications for our understanding of how immune responses are coordinated within the body. By uncovering these mechanisms, scientists could potentially design new strategies to improve the recruitment of immune cells to specific sites, such as tumor cells or areas of infection.
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