Dendritic Cells Reprogram Their Genes to Enhance Immune Response

Scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), under the leadership of Professor Francisco Sánchez-Madrid, have discovered that dendritic cells, responsible for triggering targeted immune responses, possess the ability to modify their genes in order to enhance their immune reactivity.

Dendritic Cells Reprogram Their Genes to Enhance Immune Response

Image Credit: Centro Nacional de Investigaciones Cardiovasculares

The outcomes of this research, financially supported by the Fundación “la Caixa” and unveiled in Science Advances, hold significant potential for advancing novel vaccination and immunotherapy techniques. Dendritic cells, as proficient antigen-presenting cells, play a pivotal role in kickstarting tailored or targeted immune responses.

As described by the research team, “dendritic cells capture possible pathogenic agents in different tissues and entry sites, process their components, and transport them to lymph nodes.

Here, they establish communication with T lymphocytes through the formation of a specialized structure called the immune synapse. The immune synapse allows the dendritic cell to present processed components of the infectious agent to a T cell, so that they can be recognized and initiate a specific T cell immune response.”

Previously, the primary role attributed to dendritic cells was the activation of T lymphocytes. Nevertheless, Professor Francisco Sánchez-Madrid’s team, in collaboration with Dr Almudena R. Ramiro’s group, has unearthed that dendritic cells also receive input from T cells via the immune synapse.

The T cell sends instructions that induce a change in the dendritic cell’s gene-expression program, promoting the expression of genes related to motility, antiviral responses, and secretion and thereby increasing the dendritic cell’s capacity to generate protective anti-pathogen immune responses.”

Francisco Sánchez-Madrid, Professor, Centro Nacional De Investigaciones Cardiovasculares

This study describes how gene-expression changes are accompanied by changes in epigenetic marks on DNA. These epigenetic marks in turn produce transient changes in specific genes that promote or hinder their expression,” explained first authors Irene Fernández Delgado and Diego Calzada Fraile.

One of the genes showing increased expression and enhanced accessibility is Ccr7, responsible for encoding a cell migration receptor on the surface of dendritic cells, directing them toward lymph nodes.

The research team has observed that following their engagement in an immune synapse, dendritic cells exhibit heightened efficiency in migrating to lymph nodes, where the majority of processes related to the initiation of specific or adaptive immune responses occur.

This new study, conducted in close collaboration with the CNIC Bioinformatics Unit, overseen by Manuel Gómez and Fátima Sánchez-Cabo, as well as the Genomic Unit headed by Ana Dopazo, sheds light on a novel mechanism elucidating how dendritic cells enhance their antiviral and immune activation capabilities.

The research findings lead the researchers to the conclusion that dendritic cells, which play a key role in triggering specific immune responses, undergo gene reprogramming facilitated by changes in their epigenetic DNA marks following interaction with a corresponding T cell.

These changes improve their motility, so that they arrive sooner at immune response activation sites, representing a new mechanism for potentiating the immune response.”

Furthermore, these findings hold promise for novel approaches in the advancement of vaccination and immunotherapy strategies. For instance, the elucidated mechanism could be harnessed to produce highly migratory post-synaptic dendritic cells, capable of eliciting more robust and efficient immune responses.

Source:
Journal reference:

Alcaraz-Serna, A., et al. (2023) Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells. Science Advances. doi.org/10.1126/sciadv.abb9965.

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