Study uncovers how lymphatic endothelial cells assist in generating robust immune memory

A study published today in Nature Communications describes how lymphatic endothelial cells assist in generating robust immune memory, offering new insights into how the immune system functions.

Specifically, the researchers found there is a particular genetic program within the lymphatic endothelial cells that enables storage and archival of portions of an immunization or pathogen (antigens) for future use.

The research is among the first to outline that there's a genetic "transcriptional" program within lymphatic endothelial cells that impact the immune response and could be manipulated.

The study was led by researchers from the University of Colorado Anschutz, with experts in medicine, immunology and microbiology and biochemistry and molecular genetics.

Lymphatic endothelial cells are a unique and often overlooked cell type. For a long time, we didn't fully understand the function of lymphatic endothelial cells and because of that, we underestimated the potential impact these cells have on the immune response. But we now know lymphatic endothelial cells have a distinct genetic program that plays an important role in shaping immune memory."

Beth Tamburini, PhD, senior author, associate professor of medicine, CU Anschutz School of Medicine

Using advanced machine learning techniques, the researchers were able to identify the genetic program - a specific set of genes and instructions that guide how these cells function. This allowed them to predict how effectively lymphatic endothelial cells can store antigens, which are the molecular "fingerprints" of viruses, bacteria or vaccines. When these cells archive an antigen, they're essentially saving it like a memory file, helping the immune system quickly recognize and respond to future threats. This was led by Ryan Sheridan, PhD, first author and senior research instructor at the CU Anschutz RNA Biosciences Initiative.

"If we want to improve how to combat diseases, we first need to fully understand how immune memory works. A stronger understanding of the cellular programs that control lymphatic endothelial cells, can assist in developing methodology to fine-tune immune memory, making more targeted, more durable and ultimately more effective vaccines and therapies to protect against diseases," explained Tamburini, who also serves as the immunology graduate program co-director at CU Anschutz.

To study this, Tamburini and her team used very detailed, large-scale data to better understand how the individual cells behave.

Specifically, they used single-cell RNA sequencing, which shows exactly which genes are active in each individual cell in response to immune stimuli. They also used spatial transcriptomics and analyzed genetic activity across multiple time points, giving a more dynamic view of what's happening in the cells over time regionally.

"This study stands apart because we didn't just take a snapshot, we followed these cells over time and actively manipulated the system to see how they respond," said Tamburini. "By combining cutting-edge technologies with long-term analysis and experimental intervention, we were able to uncover insights that previous short-term, observational studies couldn't. This kind of approach hasn't really been done before in this context."

The authors note this genetic transcriptional program can be used to predict immune memory potential across different diseases and even in different organisms (humans and animals).