Researchers reveal a crucial process in the working of the immune system

VIB researchers show how dendritic cells mature without causing an immune response

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Ghent, 15 May – For our immune system to initiate a response to an infection, cells called dendritic cells have to present antigens to T cells. This shows the T cells where to focus their efforts and helps clear the infection. In normal conditions, however, dendritic cells shouldn't activate the immune system or else autoimmune conditions arise. New work by the teams of profs. Yvan Saeys, Kodi Ravichandran, Bart Lambrecht, and Sophie Janssens (VIB-UGent Center for Inflammation Research) reveals how dendritic cells mature without causing an immune response. Their work appears in Science Immunology and has ramifications for the treatment of various autoimmune disorders.  

Raising the flag (in peacetime) 

Think of the immune system as an army with regiments of different cell types that have to work together to protect the rest of the body from bacterial or viral invaders. T cells are a group of diverse cells that we can consider as the infantry of our immune army. But they have to learn how to recognize the invaders first. 

That's where the dendritic cells (or DCs) come in. DCs function a bit like spies; they venture onto the battlefield, steal little pieces of the invaders (antigens) and bring them back to the T cells. Then, with these antigens, the T cells have the information they need to recognize, target, and destroy the invading bacteria or viruses. After finding and presenting antigens, DCs undergo a process of maturation. 

Even when our body is in peacetime, dendritic cells mature, which helps prevent autoimmune reactions. This is called tolerogenic maturation. How it works, though, is a mystery. Until now. 

Victor Bosteels (VIB-UGent), co-first author of the study: "The pathways driving immunogenic maturation in response to infectious insults are well-characterized, but the signals that drive tolerogenic maturation during homeostasis are still poorly understood. So, we decided to map the molecular processes that drive tolerogenic DC maturation." 

Engulfment and cholesterol 

First, the researchers confirmed that, indeed, DCs undergo maturation without being exposed to infectious stimuli in mouse models. Digging deeper, they also figured out how that process takes place. 

Sandra Maréchal (VIB-UGent), co-first author: "We found that the engulfment of apoptotic cells – cells that die as a normal part of bodily maintenance, so to speak – is necessary and sufficient to trigger DC maturation. By using a single-cell technology called CITE Seq, we unraveled the genetic program behind this process and discovered that maturing DCs activate genes that help them remove cholesterol from inside their cell bodies." 
Summary figure of the findings. Created with BioRender.com.
Summary figure of the findings. Created with BioRender.com.

With this knowledge of DC maturation in hand, the researchers took it one step further and they figured out how to mimic this process. By 'feeding' DCs empty lipid nanoparticles they could kickstart the maturation process, which suggests that the uptake of exogenous lipids, rather than the process of engulfment, is sufficient to drive the maturation program. 

Prof. Sophie Janssens (VIB-UGent), who led the study: "Our work has important implications for our understanding of the immune system in autoimmune conditions. We are hopeful that our research will lead to new insights into the role of dendritic cells in immune function, and ultimately to the development of new therapies for these and other diseases." 

Publication 

Bosteels, Maréchal, et al. LXR signaling controls homeostatic dendritic cell maturation. Science Immunology, 2023. 


Questions from patients  

A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: [email protected] Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address. 


Gunnar De Winter

Gunnar De Winter

Science Communications Expert, VIB

 

 

About VIB

VIB’s core mission is to generate disruptive insights in the molecular underpinning of life and to translate these actively into impactful innovations for patients and society. VIB is an independent research institute where some 1,800 top scientists from Belgium and abroad conduct pioneering basic research. As such, they are pushing the boundaries of what we know about molecular mechanisms and how they rule living organisms such as human beings, animals, plants, and microorganisms. Based on a close partnership with five Flemish universities – Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel, and Hasselt University – and supported by a solid funding program, VIB unites the expertise of all its collaborators and research groups in a single institute. VIB’s technology transfer activities translate research results into concrete benefits for society such as new diagnostics and therapies and agricultural innovations. These applications are often developed by young start-ups from VIB or through collaborations with other companies. This also leads to additional employment and bridges the gap between scientific research and entrepreneurship. VIB also engages actively in the public debate on biotechnology by developing and disseminating a wide range of science-based information. 

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