New research reveals that immune cells can independently navigate complex environments by actively shaping chemical cues, a discovery with significant implications for understanding immune responses and cancer metastasis. have.
Immune cells exhibit a higher level of self-directed mobility than previously appreciated. InFLAMES researcher Jonah Alanko has shown that these cells are more than just passive reactors to surrounding chemical signals. Instead, they actively modify these signals and skillfully navigate complex environments through self-organization.
Directional cell movement is an essential and fundamental phenomenon of life. This is an important prerequisite for personal development, vascular remodeling, immune response, etc.
The research conducted by postdoctoral researcher Jonah Alanko focused on the migration and navigation of immune cells within the body. Chemokines, a type of signaling protein, play an important role in directing immune cells to specific locations. Chemokines, for example, form in lymph nodes and create chemical cues called chemokine gradients that cells in the body follow. According to Alanko, these chemokine gradients are like scent trails left in the air, getting brighter as you move away from their source.
The traditional idea was that immune cells recognize targets according to pre-existing chemokine gradients. In other words, cells that follow these cues have been viewed as passive actors, when in fact they are not.
Dendritic cells move through a microscopic maze with the help of chemokine gradients they create. In the upper image, the nucleus of the cell is drawn in blue, and the lines in the lower image represent the movement of the cell.Credit: Jonna Alanko, University of Turku
“Contrary to previous notions, we were able to demonstrate for the first time that immune cells do not need pre-existing chemokine gradients to find their way. They can create their own gradients, making complex We can move collectively and efficiently even in difficult environments,” Alanko explains.
cells consume chemokines
Immune cells have receptors that can sense chemokine signals. One of these receptors is called CCR7 and is present on dendritic cells.
Dendritic cells are specialized antigen-presenting cells that have a critical role in activating the overall immune response. We need to find the infection, recognize it, and then move to the lymph nodes with that information. In lymph nodes, dendritic cells interact with other cells of the immune system to mount an immune response against pathogens.
Alanko’s research showed that dendritic cells not only register chemokine signals at the CCR7 receptor, but also actively shape their chemical environment by consuming chemokines. The cells thereby create local gradients that guide their own movement and that of other immune cells. The researchers also discovered that another type of immune cell, her T cells, can benefit from these self-generated gradients to enhance their own directional movement.
“When immune cells are able to create chemokine gradients, they can guide the directional movement of themselves and other immune cells to avoid future obstacles in complex environments,” explains Jonah Alanko. do.
This discovery deepens our understanding of how immune responses are regulated in the body. But it can also reveal how cancer cells direct their movement to cause metastasis.
“The CCR7 receptor has also been found in many types of cancer, and in these cases this receptor has been shown to promote cancer metastasis. Cancer cells use the same mechanisms as immune cells to It may even guide its movement. Our findings therefore have the potential to help design new strategies not only to target specific cancers but also to modify immune responses. ,” said Jonah Alanco.
Reference: “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective migration of leukocytes” Jonna Alanko, Mehmet Can Uçar, Nikola Canigova, Julian Stopp, Jan Schwarz, Jack Merrin, Edouard Hannezo, Michael Sixt, September 1, 2023; scientific immunology.
DOI: 10.1126/sciimmunol.adc9584
Jonna Alanko is a postdoctoral researcher at the InFLAMES Flagship in the MediCity laboratory at the Faculty of Medicine, University of Turku, Finland. She carried out most of her recently published research in a research group led by Professor Michael Sixt at the Austrian Institute for Science and Technology (ISTA) in Austria.
Source: scitechdaily.com
