The figure shows the complicated company of dendritic cells in the lymph node. Capillary are displayed in blue. The cells in green are young dendritic cells whereas the dendritic cells in red are a few days older and have actually currently moved. The dendritic cells in orange are intermediate in age. Credit: Dr. Milas Ugur/ University of Würzburg
Scientists have discovered how brief dendritic cells of the body immune system type three-dimensional networks, using capillary as guides. These networks, controlled by local cytokines, play an essential role in immune defense and hold high prognostic value for growth illness. Further study intends to see if these principles use universally across tissues and in human beings.
The Role of the Immune System and Immune Cells
The cells of the immune system distribute primarily in the blood and move into the bodys tissues after an inflammation. Some types of immune cells, however, are permanently located in the tissues, where they come together to form three-dimensional networks.
How do these networks form and how are they maintained? For the long-lived macrophages (phagocytes), the answer is already understood: They settle in so-called specific niches. These are environments of connective tissue cells that provide the macrophages with nutrients and keep them alive.
The figure shows the intricate organization of dendritic cells in the lymph node. The cells in green are young dendritic cells whereas the dendritic cells in red are a couple of days older and have currently migrated. Researchers have found how short-term dendritic cells of the immune system kind three-dimensional networks, using blood vessels as guides. The cytokines are continuously and uniformly produced in your area and consumed by the dendritic cells. If there are gaps in the group, more cytokines are offered for the isolated dendritic cells.
A Closer Look at Dendritic Cells
A team led by Professors Georg Gasteiger, Dominic Grün, and Wolfgang Kastenmüller from the Institute of Systems Immunology at Julius-Maximilians-Universität Würzburg (JMU)/ Max Planck Research Group has actually now turned its attention to an associated kind of immune cells, the so-called dendritic cells.
These immune cells are important for the control of immune reactions due to the fact that they are at the first line of defense of the body immune system: They recognize foreign structures, take them in and process them into a sort of mugshot. They then provide the photo to other immune cells and trigger a specific immune action, for example versus pathogens or cancer cells.
Dendritic Cells Migrate Through the Tissue
The unique feature of dendritic cells is they just live for about a week and throughout this time they continually move through the bodys tissues. “In this respect, it was clear that the traditional niche idea would not work here,” says Wolfgang Kastenmüller.
The JMU team found an entirely brand-new principle for this, according to which three-dimensional cell networks can arrange themselves: Dendritic cells orient themselves to the blood vessels and migrate one after the other along their external wall– comparable to children strolling in single file. The blood vessels therefore determine the three-dimensional arrangement of the cells.
Role of Cytokines in Network Regulation
” We wished to understand how this procedure is controlled and how the cells handle to close gaps in their network,” explains Dr. Milas Ugur, a scientist in Professor Kastenmüllers group. Since otherwise the immune defense no longer functions optimally, closing such gaps is important.
As the JMU group reports in the journal Immunity, it is due to an in your area acting cytokine, the FLT3 ligand, that the dendritic cells always stay close together during their developmental migration.
The cytokines are continually and uniformly produced locally and consumed by the dendritic cells. If there are gaps in the group, more cytokines are readily available for the isolated dendritic cells.
Prognostic Significance for Tumor Diseases
These findings are for example crucial for cancer treatment: dendritic cells have a high prognostic value for growth diseases: The greater their abundance in the growth, the much better the prognosis for the patient. This is specifically real after immunotherapy.
” Increasing our fundamental insights on dendritic cell biology will help us to bring back the networks of these cells in growths and thus tailor ideal treatments in the future” describes Kastenmüller.
Next Steps in the Research
The JMU researchers information up until now is based on the analysis of lymph nodes from animal designs. The team next wants to evaluate whether the exact same principles of network organization of dendritic cells use to all tissues and also in humans.
Reference: “Lymph node medulla manages the spatiotemporal unfolding of resident dendritic cell networks” by Milas Ugur, R. Jacob Labios, Chloe Fenton, Konrad Knöpper, Katarzyna Jobin, Fabian Imdahl, Gosia Golda, Kathrin Hoh, Anika Grafen, Tsuneyasu Kaisho, Antoine-Emmanuel Saliba, Dominic Grün, Georg Gasteiger, Marc Bajénoff and Wolfgang Kastenmüller, 17 July 2023, Immunity.DOI: 10.1016/ j.immuni.2023.06.020.
The work explained was performed in cooperation with scientists from the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI) and with researchers from France and Japan.
Immunology in Würzburg.
Würzburg University Medical Center has actually distinguished itself as an important research study location in the field of immunology and has actually greatly broadened these proficiencies in current years. In numerous institutes and chairs, scientists are dealing with much better comprehending the immune system and utilizing it to combat diseases. In doing so, they work together closely with other scientists in Germany and worldwide.
