An illustration depicts the intricate arrangement of dendritic cells within the lymph node. The blue structures represent blood vessels. The dendritic cells highlighted in green are new, while those marked in red have aged a few days and migrated. The orange dendritic cells indicate an intermediate age. This image is credited to Dr. Milas Ugur from the University of Würzburg.
Scientists have unraveled the method through which the fleeting dendritic cells of the immune system construct 3D networks, utilizing blood vessels as their guiding structures. These networks, controlled by local cytokines, serve a pivotal role in the body’s immune defense and bear significant prognostic potential for cancer. Ongoing research strives to determine whether these principles are universally applicable across various tissues and in humans.
Understanding the Immune System and Its Cells
Primarily circulating in the blood, immune cells migrate into the body tissues upon inflammation. Some immune cells, however, permanently reside in these tissues, forming 3D networks.
How are these networks established and sustained? The long-lasting macrophages, or phagocytes, already have an answer: they settle into ‘niches’ – connective tissue cell environments providing nutrients and prolonging their lifespan.
Investigating 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 shifted focus to dendritic cells, another class of immune cells.
Dendritic cells are pivotal for managing immune responses, functioning as the immune system’s first line of defense. They identify foreign structures, ingest them, and convert them into a kind of identification profile. They then share this profile with other immune cells, instigating a targeted immune response, often against pathogens or cancer cells.
The Migration of Dendritic Cells
A unique attribute of dendritic cells is their lifespan of about a week, during which they constantly traverse the body tissues. “It was clear that the classic niche concept wouldn’t apply here,” states Wolfgang Kastenmüller.
The JMU team has uncovered a new concept wherein dendritic cells can self-organize into 3D networks. They use blood vessels as their reference, migrating sequentially along their external wall, mirroring children walking in a single file line. The blood vessels hence determine the spatial organization of the cells.
Role of Cytokines in Regulating Networks
“We wanted to understand how this process is controlled and how the cells manage to fill the gaps in their network,” elaborates Dr. Milas Ugur, a scientist in Professor Kastenmüller’s group. Filling such gaps is crucial as it ensures optimal immune defense.
As revealed in the journal Immunity by the JMU team, a locally active cytokine, FLT3 ligand, ensures the dendritic cells remain closely packed during their migratory journey. Cytokines, produced and consumed locally and evenly by the dendritic cells, expedite the development and movement of isolated dendritic cells when gaps emerge, enabling them to rejoin the group. Upon rejoining, the cells slow down due to the competitive absorption of cytokines by neighboring cells.
Cancer Prognosis and Dendritic Cells
These findings bear relevance to cancer therapy, as dendritic cells offer considerable prognostic value for cancer. Greater their presence in the tumor, more favorable is the prognosis for the patient, particularly post immunotherapy.
“Enhancing our fundamental understanding of dendritic cell biology will assist in reestablishing these cell networks within tumors, ultimately aiding in developing personalized therapies in the future,” explains Kastenmüller.
Future Research Directions
So far, the data from the JMU researchers is based on the analysis of lymph nodes from animal models. The team plans to investigate whether the principles of dendritic cell network organization apply universally across tissues and also in humans.
The research, detailed in “Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks” by Milas Ugur, et al., was published on 17 July 2023, in the Immunity journal. DOI: 10.1016/j.immuni.2023.06.020
This work was executed in partnership with researchers from the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI) and scientists from France and Japan.
Immunology Research in Würzburg
The Würzburg University Medical Center has emerged as a significant immunology research hub, significantly expanding its competencies over the recent years. Scientists across several institutes and chairs strive to comprehend the immune system better and harness it to combat diseases, collaborating closely with other researchers, both domestically and internationally.
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Table of Contents
Frequently Asked Questions (FAQs) about Dendritic Cells 3D Networks
What are dendritic cells and their role in the immune system?
Dendritic cells are a type of immune cell responsible for controlling immune responses. They act as the first line of defense by identifying foreign structures, processing them, and triggering specific immune responses against pathogens or cancer cells.
How do dendritic cells form 3D networks?
Dendritic cells form 3D networks by utilizing blood vessels as guides. They migrate sequentially along the outer walls of blood vessels, similar to children walking in single file, allowing the blood vessels to determine their spatial arrangement.
What regulates the formation of dendritic cell networks?
Local cytokines, particularly the FLT3 ligand, play a crucial role in regulating dendritic cell networks. These cytokines are continuously produced and consumed by the dendritic cells, helping them stay closely packed during their migratory journey.
What is the significance of dendritic cell networks for cancer prognosis?
Dendritic cells have a high prognostic value for tumor diseases, especially after immunotherapy. The abundance of dendritic cells in the tumor is positively correlated with better prognoses for patients.
How can these findings impact cancer therapy?
Understanding dendritic cell biology can aid in developing personalized therapies for cancer by restoring dendritic cell networks within tumors, thereby enhancing immune responses against cancer cells.
More about Dendritic Cells 3D Networks
- University of Würzburg – Institute of Systems Immunology
- Journal Article – “Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks”
- Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI)
- Immunity Journal
