3rd September 2023,Mumbai: Our immune system is a remarkable network of cells and molecules working together to protect our body from infections and diseases. Dendritic cells (DCs), often referred to as the “sentinels” of the immune system, play a crucial role in this defense mechanism. A recent study published in Science Immunology has unveiled fascinating insights into the migration of dendritic cells, shedding light on the intricate dance of immune cells in response to chemokines and cell density.
Dendritic Cells: The Bridge Between Innate and Adaptive Immunity
Dendritic cells are the unsung heroes of our immune response. They act as intermediaries between the immediate, innate response, and the more targeted, adaptive response. These cells function like detectives, tirelessly patrolling our tissues to detect signs of infection or intrusion. Once they identify a threat, dendritic cells embark on a journey to the lymph nodes, where they share vital information and kickstart the subsequent phases of the immune cascade.
Chemokines: Guiding the Migration of Immune Cells
Chemokines, tiny signaling proteins produced by lymph nodes, act as compasses for immune cells like dendritic cells. These molecules create a gradient that directs the migration of immune cells towards the lymph nodes. Initially, it was believed that immune cells moved towards higher chemokine concentrations as directed by this extrinsic gradient. However, a recent study conducted by the Institute of Science and Technology Austria (ISTA) has challenged this conventional wisdom.
The Role of CCR7: A Key Player in Immune Cell Migration
In their research, the scientists at ISTA delved into the role of CCR7, a surface feature present on activated dendritic cells. CCR7’s primary function is to bind to CCL19, a molecule specific to lymph nodes, which triggers subsequent immune response stages. What the researchers discovered was groundbreaking—CCR7 not only senses CCL19 but actively shapes the distribution of chemokine concentrations.
Internalization of Chemokines by Dendritic Cell
Through a series of experiments, the researchers demonstrated that migrating dendritic cells actively take up and internalize chemokines via the CCR7 receptor. This process results in a localized reduction of chemokine concentration in their immediate surroundings. Consequently, dendritic cells move towards areas with higher chemokine concentrations, where fewer signaling molecules are present.
The Collective Nature of Immune Cell Migration
What makes this discovery even more intriguing is the collective nature of immune cell migration. Immune cells, thanks to their dual function, can produce their own guidance cues. This phenomenon enhances the coordination of their group migration. To gain a deeper understanding of this mechanism at the multicellular scale, the researchers collaborated with theoretical physicists Edouard Hannezo and Mehmet Can Ucar from ISTA.
Computer Simulations: Unraveling the Complexity of Cell Dynamics
Together with their physicist colleagues, Alanko and her team developed computer simulations that replicated their experimental findings. These simulations helped them hypothesize that dendritic cell migration is influenced by two crucial factors: the density of the cell population and individual responses to chemokines. The more cells present, the sharper the chemokine gradient they generate.
Beyond Dendritic Cells: Impact on T-Cell Movement
Intriguingly, this dynamic interplay between cell populations doesn’t just affect dendritic cells. T-cells, the immune cells responsible for annihilating harmful germs, also benefit from this mechanism to enhance their directional movement. This revelation opens new doors for further exploration and understanding of the intricate interactions between various immune cell populations. The recent study on dendritic cell migration has uncovered a previously hidden layer of complexity in our immune system’s response to infections. This research not only deepens our understanding of immune cell behavior but also has the potential to pave the way for novel therapeutic approaches in immunology. As we continue to unravel the mysteries of the immune system, we may find new ways to harness its power to combat diseases more effectively.
-by Kashvi Gala