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Updated: May 2, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
A restarted life: Resetting microglia innate immune memory
Fangyuan Cheng1, Bo Yan2, Fanglian Chen3
1Department of Geriatrics, Tianjin Medical University General Hospital, Anshan Road No. 154, Tianjin 300052, China; Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Ministry of Education, Tianjin, 300052, China.
Abstract:
Microglia can achieve depletion and repopulation through various mechanisms, improving outcomes in multiple CNS diseases. Innate immune memory in microglia can undergo continuous reprogramming through epigenetics, facilitating iterative memory upgrades. Here, through a comprehensive literature review, we propose the concepts of the microglial innate immune memory prototype (MIIMP) and microglial temporally phased innate immune memory reset (MTPIIMR). The temporally phased innate immune memory are reflected not only in the formation of immune response prototypes in microglia but also in the partial reset of innate immune memory during the depletion and repopulation process. In the duel against time, single cycles of depletion and repopulation can yield benefits through partial innate immune memory reset, while multiple cycles accelerate microglial aging. Identifying the optimal solution to replace microglia for filling ecological niches and executing their functions perfectly is a formidable yet profoundly significant challenge.
Insights
Microglia
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the resident immune cells of the central nervous system (CNS), play critical roles in brain health and disease.
- Their functions, including innate immune memory, can be modulated through epigenetic reprogramming.
- Understanding microglial dynamics is crucial for developing effective CNS disease therapies.
Purpose of the Study:
- To introduce novel concepts regarding microglial innate immune memory and its temporal dynamics.
- To explore the implications of microglial depletion and repopulation on immune memory and aging.
- To highlight the challenge of optimizing microglial replacement strategies for CNS diseases.
Main Methods:
- Comprehensive literature review of microglial biology, innate immunity, and CNS disease mechanisms.
- Conceptualization of the microglial innate immune memory prototype (MIIMP).
- Development of the microglial temporally phased innate immune memory reset (MTPIIMR) framework.
Main Results:
- Proposed MIIMP and MTPIIMR as key frameworks for understanding microglial memory.
- Demonstrated that single depletion-repopulation cycles can benefit from partial memory reset.
- Identified that multiple cycles accelerate microglial aging, impacting CNS disease outcomes.
Conclusions:
- Microglial innate immune memory is dynamic and subject to temporal reprogramming.
- Partial reset of microglial innate immune memory during repopulation offers therapeutic potential.
- Optimizing microglial replacement is a significant challenge for treating CNS disorders.
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