▎ WuXi AppTec content team editor
By stacking a large pile of stones tightly layer by layer, we can get a tight stone wall. Similarly, in our bodies, cells are tightly arranged to form dense tissues that resemble walls. At this point, for immune cells swimming between tissues, this "wall" seems to block their way, making it difficult for them to enter the tissue.
But we know that the immune cells in our bodies are not tied up. They must have found a special path to travel through dense cellular tissues and respond to immune responses. This week, a new study published in Science found the answer, revealing the entire process by which immune cells enter the tissue. It is worth mentioning that three of the authors of this paper are also local high school students, who also contributed to the study.
To study this process, a team led by Professor Dalia E. Siekhaus of the Austrian Institute of Science and Technology chose fruit flies as the subject of study. What they wanted to observe was how drosophila's important immune cells, macrophages, entered their embryos.
Early in the embryonic development of Drosophila, macrophages follow the guiding signaling molecules to the junction of the embryonic ectoderm and mesoderm. Here, macrophages encounter obstacles in the formation of embryonic cells in tight alignment. What you see under the microscope, however, is that these macrophages are lined up in long lines, like a long chain slowly passing through the gaps in the tissues and entering the tissues. So, how do these macrophages, especially the first cells, break through the barrier?
▲ Macrophages (magenta) migrate in Drosophila embryos, and blue dots indicate embryonic cells that are about to divide (Image: Maria Akhmanova)
Professor Siekhaus's team tracked this process under a high-resolution microscope and found that when the first macrophages reached the entrance, it waited for a special period: the ectoderm cells in front of them first rounded and morphologically resembled spherical before undergoing mitosis. At this point, the connection of ectoderm cells to the surrounding matrix (i.e., sticky plaques) is significantly weakened.
For the leading macrophage, this is exactly the breakthrough it is looking forward to. Macrophages move the nucleus to the front of the cell and thus move forward, entering the embryonic tissue from the weak zone between the ectoderm and mesoderm. As the first macrophage entered, the other macrophages waiting in line found their way, following their companions in front of them.
▲ The process of macrophages entering the embryonic tissue (Image source: Maria Akhmanova)
For the researchers, there is still a question that remains unexplained: what really causes macrophages to enter is the morphological change of the cell, or the weakening of the cell connection?
To solve this problem, they used optogenetics to induce genetic changes related to cell morphology and cell connections, respectively. As a result, just the fact that cells becoming spherical is not enough to allow macrophages to enter; conversely, artificially reducing cell connections through genetic mutations allows macrophages to enter.
When macrophages enter, the ectoderm cells in front of them turn round (Image: Maria Akhmanova)
In a recent study, Professor Siekhaus's team also revealed more findings about this process. For example, to get through the barrier, a nuclear protein called Atossa provides energy to the macrophages that take the lead; in addition, to avoid nucleus damage, macrophages also form a protection made of actin fibers.
"Cell division is a key process that controls the entry of macrophages into tissues, and this elegant concept has a powerful impact." Professor Siekhaus said.
The mechanism by which macrophages enter tissues may also be critical to other types of immune cells. Therefore, the discovery is also expected to help scientists understand more physiological processes: whether manipulating the connection or division of tissue cells helps immune cells invade, fight tumors, or help weaken the ability of immune cells to attack tissues during autoimmunity.
In addition to scientists from the Austrian Institute of Science and Technology and the European Molecular Biology Laboratory, the authors of this paper are three small authors at Kloster Neuburg High School in Austria. During their visit to the Siekhaus lab, they were involved in fruit fly-related experiments and wrote code to help speed up image analysis. As Dr Maria Akhmanova, the paper's first author, put it: "The success of this project was inseparable from the collaboration of numerous scientists and three enthusiastic high school students. ”
Resources:
[1] Maria Akhmanova et al. 2022. Cell division in tissues enables macrophage infiltration. Science. DOI: 10.1126/science.abj0425
[2] Dividing walls: How immune cells enter tissue. Retrieved Apr. 21, 2022 from https://www.eurekalert.org/news-releases/950073
More recommendations
Click "Watching" and go again