Introduction

The human immune system plays a vital role in protecting our bodies from various diseases and infections. When faced with an immunological threat, such as germs or toxins, immune cells need to quickly identify and reach their target. Researchers from the Austrian Institute of Science and Technology (ISTA) conducted a study that challenges previous notions about how immune cells navigate through complex environments. The findings of their research, published in the journal “Immunology Science,” not only enhance our understanding of the immune system but also offer potential new approaches to improve the human immune response.

The Coordinated Movement of Immune Cells

During infection and inflammation, immune cells demonstrate a coordinated collective movement. However, the question of how these cells know which way to go has remained a mystery. To address this question, a group of scientists from the ISTA delved into the ability of immune cells, specifically dendritic cells (DCs), to collectively migrate through complex environments.

Dendritic Cells: The Messengers

Dendritic cells are key players in our immune response. They act as messengers between the innate and adaptive responses, scanning tissues for intruders and relaying important information to other immune cells. Traditionally, it was believed that dendritic cells and other immune cells moved toward higher concentrations of a signaling protein called chemokines, which were released by lymph nodes. However, the recent research conducted at ISTA challenges this notion.

Receptor CCR7: A Dual Function

The scientists at ISTA focused on a specific receptor called CCR7 found on activated dendritic cells. This receptor not only detects a specific molecule in the lymph nodes but also actively contributes to shaping the distribution of chemokine concentrations. By taking up and internalizing chemokines through the CCR7 receptor, dendritic cells create a local depletion of chemokine concentration. This depletion results in the cells moving toward areas with higher chemokine concentrations, allowing them to generate their own guidance signals.

Understanding the Mechanism on a Multicellular Scale

To gain a deeper understanding of this mechanism, the researchers at ISTA collaborated with theoretical physicists Edouard Hannezo and Mehmet Can Ucar. By using computer simulations, they reproduced the experiments and predicted that the movement of dendritic cells depends not only on individual responses to chemokines but also on the density of the cell population. This collective nature of cell migration highlights the complexity and coordination involved in immune responses.

Benefiting T Cells

The research also revealed that T cells, another type of immune cells responsible for destroying harmful germs, benefit from the dynamic interaction between dendritic cells and chemokines. This interaction enhances the directional movement of T cells, further emphasizing the interconnectedness of different immune cell populations within the body.

Implications for Improving Immune Responses

The discoveries made by the ISTA researchers challenge previous assumptions about how immune cells respond to chemokines and actively shape their own environment. This dynamic regulation of signaling signals provides an elegant strategy for immune cells to guide their own movement and that of other immune cells. The implications of this research are significant for understanding how immune responses are coordinated within the body.

Enhancing Cell Recruitment

By understanding the mechanisms behind immune cell migration, scientists could devise new strategies to enhance the recruitment of immune cells to specific sites, such as tumor cells or areas of infection. This knowledge could lead to advancements in the development of therapeutic approaches that optimize the body’s immune response against various diseases.

Summary

Researchers from the Austrian Institute of Science and Technology (ISTA) have discovered that immune cells actively generate their own guidance system to navigate through complex environments. Contrary to previous notions, immune cells not only respond to external chemokine gradients but also actively shape their environment by consuming these chemical signals. This dynamic regulation of signaling signals allows immune cells, such as dendritic cells, to more effectively orchestrate their collective migration. The findings of this research published in the journal “Immunology Science” improve our understanding of the immune system and offer potential new approaches to improve human immune responses. By further exploring the mechanisms behind immune cell migration, scientists can explore strategies to enhance the recruitment of immune cells to specific sites, ultimately leading to advancements in therapeutic approaches against diseases.

Immunological threats, such as germs or toxins, can arise in all parts of the human body. Fortunately, the immune system (our own protective shield) has its intricate ways of dealing 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 way to go?

A group of scientists from the Sixt group and the Hannezo group from the Austrian Institute of Science and Technology (ISTA) addressed this question. In their study, published today in scientific immunologyresearchers shed light on the ability of immune cells to collectively migrate through complex environments.

Dendritic cells: the messengers

Dendritic cells (DCs) 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 future infections). Like detectives, DCs scan tissue for intruders. Once they locate a site of infection, they are activated and immediately migrate to the lymph nodes, where they deliver 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) that establish a gradient. In the past, it was believed that DCs and other immune cells reacted to this external gradient and moved towards a higher concentration. However, new research conducted at ISTA now challenges this notion.

One receiver, two functions

The scientists took a close look at one 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 of the immune response. “We found that CCR7 not only detects CCL19, but also actively contributes to shaping the distribution of chemokine concentrations,” explains 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 through the CCR7 receptor, resulting in a local depletion of chemokine concentration. With fewer signaling molecules around, they move toward higher chemokine concentrations. This dual function allows immune cells to generate their own guidance signals to more effectively orchestrate their collective migration.

The movement depends on the cell population.

To quantitatively understand this mechanism on a multicellular scale, Alanko and his colleagues partnered with theoretical physicists Edouard Hannezo and Mehmet Can Ucar, also at ISTA. Using their expertise in cell motion and dynamics, they set up computer simulations that were able to reproduce Alanko’s experiments. With 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 steeper the gradient they generate. It really highlights the collective nature of this phenomenon!” says Can Úcar.

Furthermore, the researchers found that T cells (specific immune cells that destroy harmful germs) also benefit from this dynamic interaction to enhance their own directional movement. “We are eager to learn more about this new principle of interaction between cell populations with ongoing projects,” continues the physicist.

Improve immune response

The discoveries are a step in a new direction for how cells move within 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 important implications for our understanding of how immune responses are coordinated within the body. By discovering these mechanisms, scientists could devise new strategies to improve the recruitment of immune cells to specific sites, such as tumor cells or areas of infection.