New clues on immune memory revealed by epigenetic studies

The immune system is a marvel of complexity, safeguarding our health by eliminating harmful invaders like parasites, viruses, and bacteria, while also targeting damaged and cancerous cells. One of its most fascinating features is its memory, allowing it to respond more quickly upon subsequent encounters with antigens.

In a recent groundbreaking study led by Dr. Ralph Stadhouders from Erasmus MC and Dr. Gregoire Stik from the Josep Carreras Leukemia Research Institute, new insights into immune memory have emerged. Published in the journal Science Immunology, the research led by Anne Onrust-van Schoonhoven and her team compared the response of “naïve cells” (those never exposed to an antigen) with “memory cells” that had prior exposure to an antigen, displaying a more rapid activation pattern.

The investigation delved into the epigenetic control of cellular machinery and the nuclear architecture of the cells, two potential mechanisms behind the memory phenomenon. Despite cells in an individual carrying the same genetic information, different cell types access different parts of the DNA, regulated by epigenetic mechanisms.

The research uncovered a distinct epigenetic signature in memory cells, leading to the rapid activation of crucial genes compared to naïve cells. These genes became more accessible to cellular machinery, particularly the AP-1 family of transcription factors, indicating that they have been “warmed-up” since the cell’s first antigen contact.

Additionally, the spatial distribution of DNA within the nucleus differed between naïve and memory cells. Key genes responsible for the early immune response were clustered together and influenced by the same regulatory regions called enhancers. In essence, these genes were not only “warmed-up” but also gathered at the starting line, ready to act swiftly.

Excitingly, the research extended beyond healthy cells. In studying immune cells from chronic asthma patients, the team found that circuits crucial for an early and robust immune response were overactivated.

These findings not only deepen our understanding of the immune system’s intricacies but also hold promise for advancing the field of epigenetic drugs and treatments. In particular, such discoveries may pave the way for targeting autoimmune diseases and cancer with greater precision and efficacy. The future of epigenetic control in the immune system looks promising, thanks to the pioneering work of Dr. Stik and his colleagues.

Source: Josep Carreras Leukaemia Research Institute

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