Unveiling How Dendritic Cells Respond to mRNA Vaccines

Recent research conducted by Belgian scientists has shed light on the intricate ways the immune system responds to mRNA vaccines. Central to this process are dendritic cells, which act as early detectors of viral infections like viruses and bacteria. These cells play a crucial role in orchestrating the immune response by alerting T cells to eliminate threats. Interestingly, dendritic cells can adopt different roles—some remain in a balanced, homeostatic state, while others become highly immunogenic, actively triggering immune attacks.

The investigators focused on understanding how these cells react when exposed to lipid nanoparticles (LNPs), the delivery technology used in mRNA vaccines. LNPs are tiny spheres designed to ferry genetic instructions into immune cells, prompting them to produce specific viral proteins and stimulate immunity. Using advanced techniques such as CITE-sequencing and flow cytometry, researchers observed that LNPs could influence dendritic cells to either stay in a resting, non-reactive state or become fully activated and trigger an immune response.

A key finding was that empty LNPs, without any genetic content, did not significantly activate immune responses, which is promising for vaccine safety. This suggests they can deliver vaccine components effectively without causing unnecessary inflammation. Importantly, by modifying what is loaded into these nanoparticles—whether mRNA encoding viral antigens or peptides—they can direct dendritic cells to either activate the immune system or promote tolerance. For example, LNPs carrying mRNA prompted dendritic cells to activate T cells and offer protection, whereas LNPs without genetic material supported a more tolerant, homeostatic role.

Dr. Sofie Rennen, the study's lead author, highlighted that this understanding paves the way for designing vaccines that appropriately calibrate the immune response. This could be particularly useful in developing therapies for autoimmune diseases, where calming the immune system is desirable. Professor Sophie Janssens emphasized that mapping dendritic cell responses can help create more precise and safer vaccines in the future.

The findings, published in Cell Reports, not only advance our understanding of immune responses to mRNA vaccines but also open new avenues for vaccine design—potentially leading to more effective and safer immunizations tailored to various medical needs.

Source: https://medicalxpress.com/news/2025-08-scientists-dendritic-cell-reactions-mrna.html