Trained immunity and epigenetic memory in long-term self-renewing hematopoietic cells

Area of Science:

• Immunology
• Hematology
• Epigenetics

Background:

• Immunologic memory is traditionally linked to adaptive immunity.
• Emerging evidence shows innate immune cells and hematopoietic stem cells (HSCs) can acquire long-term memory through epigenetic changes.
• This phenomenon is termed trained immunity.

Purpose of the Study:

• To summarize recent advancements in trained immunity and epigenetic memory formation.
• To focus on trained immunity in HSCs and self-renewing alveolar macrophages.
• To highlight findings from the Spring 2022 International Society for Experimental Hematology (ISEH) webinar.

Main Methods:

• Review of recent studies on epigenetic signatures in innate immune cells and HSCs.
• Analysis of changes in epigenetic landscape and chromatin accessibility in lineage-specific genes.
• Investigation of metabolic alterations contributing to trained immunity.

Main Results:

• Trained immunity in HSCs involves epigenetic modifications and metabolic shifts.
• These changes can lead to skewed lineage bias, favoring myelopoiesis.
• Epigenetically modified innate immune cells provide enhanced protection upon secondary infection.

Conclusions:

• Hematopoietic stem cells and innate immune cells exhibit a form of long-term memory.
• Trained immunity, driven by epigenetic and metabolic changes, enhances innate immune responses.
• This mechanism offers improved defense against reinfection.