Hematopoietic stem cell state and fate in trained immunity

Area of Science:

• Immunology
• Stem Cell Biology
• Epigenetics

Background:

• Trained immunity provides innate immune memory, enhancing pathogen resistance and immunosurveillance.
• Innate immune cells have short lifespans, suggesting long-term memory relies on hematopoietic stem cells (HSCs).
• HSCs undergo functional reprogramming, influencing progeny cell adaptation and innate immune plasticity.

Purpose of the Study:

• To review recent advances in understanding hematopoietic stem cell (HSC) state and fate within trained immunity.
• To elucidate the regulatory networks governing HSCs in trained immunity.
• To provide insights for developing targeted therapies against infectious diseases and chronic inflammation.

Main Methods:

• Literature review of recent advances in trained immunity and HSC biology.
• Analysis of stem cell-intrinsic and extrinsic regulatory networks.
• Synthesis of current models of innate immune memory.

Main Results:

• Trained immunity involves epigenetic and metabolic reprogramming of long-lived HSCs.
• HSCs adapt their state and fate to generate functionally diverse progeny cells.
• Both beneficial and detrimental trained immunity processes impact HSCs, leading to varied immune outcomes.

Conclusions:

• Understanding HSC regulation in trained immunity is crucial for refining innate immune memory models.
• Targeting HSCs offers potential for novel therapeutic strategies against infectious and inflammatory conditions.
• A framework for engineering precision-trained immunity via HSC interventions is proposed.