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August 16, 2026Cell Communication and SignalingOpen Access

TREM2 regulates continual efferocytosis of apoptotic neurons by monocyte-derived macrophages via AKT-PFKFB2-mediated glycolytic reprogramming after acute ischemic stroke

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Authors

JWJun WenHTHao TangQYQinghuan Yang

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Overview

Translational study demonstrates TREM2 promotes macrophage efferocytosis via glycolytic reprogramming in ischemic stroke, highlighting a therapeutic target for repair.

Key Points

  • To determine whether and how TREM2 regulates the reparative efferocytosis of apoptotic neurons by monocyte-derived macrophages following acute ischemic stroke.
  • Analyzed serum soluble TREM2 (sTREM2) levels and circulating monocyte TREM2 expression in patients with acute ischemic stroke.
  • Utilized mouse middle cerebral artery occlusion/reperfusion models with CCR2-GFP tracing, myeloid TREM2 deficiency, and adoptive transfer of TREM2-overexpressing macrophages alongside single-cell RNA sequencing and metabolomics.
  • Evaluated the effect of the TREM2 agonistic antibody AL002c in human monocyte-derived macrophages.
  • Serum sTREM2 levels in patients with stroke were elevated and positively associated with admission NIHSS scores and 90-day mRS functional disability scores.
  • Myeloid TREM2 deficiency exacerbated ischemic brain injury and neurological deficits in mice, whereas adoptive transfer of TREM2-overexpressing macrophages partially reversed the damage.
  • TREM2 promoted continual macrophage efferocytosis via SYK-dependent AKT-PFKFB2 glycolytic reprogramming, sustaining MERTK and LRP1 expression, which was recapitulated by AL002c in human macrophages.

Cite This Study

Wen et al. (2026) studied this question.

synapsesocial.com/papers/6a8179bcf2fb91fc834ad013https://doi.org/10.1186/s12964-026-03148-9
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Also Consider

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  1. 1Astrocyte‐<scp>TREM2</scp> alleviates brain injury by regulating reactive astrocyte states following ischemic stroke2024 · 13 citations
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  4. 4Soluble Triggering Receptors Expressed on Myeloid Cells (sTREM) in Acute Ischemic Stroke: A Potential Pathway of sTREM-1 and sTREM-2 Associated with Disease Severity2024
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