Work

LILRB2–TREM2 signalling as a candidate microglial checkpoint in white matter repair: an evidence-calibrated review informed by neuronal PirB

Year: 2026

Type: article

Abstract: Background White matter repair requires coordinated myelin-debris clearance, inflammatory resolution, oligodendrocyte precursor cell (OPC) differentiation, remyelination and adaptive circuit reorganization. Murine paired immunoglobulin-like receptor B (PirB) and the functionally corresponding human leukocyte immunoglobulin-like receptor B2 (LILRB2) occupy potentially important but incompletely defined positions within this sequence. Main body Direct evidence establishes neuronal PirB as a receptor for Nogo, myelin-associated glycoprotein and oligodendrocyte-myelin glycoprotein in mice, where it recruits SHP-1/2, suppresses Trk signalling and limits structural plasticity. Separately, human microglial systems show that LILRB2 can oppose TREM2–DAP12-dependent migration and phagocytosis. TREM2-dependent lipid adaptation is required for repair after demyelination, but no study has completed the causal chain from LILRB2 blockade to enhanced myelin-debris processing, OPC differentiation, ultrastructural remyelination and restored conduction. We therefore distinguish direct evidence, bridging evidence and testable predictions; prioritize multiple sclerosis as the most informative initial disease context; and define human-lesion, cell-specific, pharmacological and functional validation gates. Conclusion PirB/LILRB2 is best considered a candidate, context-dependent neuroimmune checkpoint rather than an established remyelination target. Translation requires human lesion localization, demonstration of LILRB2–TREM2 engagement with myelin-relevant ligands, cell-selective target occupancy and repair defined by lineage, ultrastructural and electrophysiological endpoints.

Source: Frontiers in Aging Neuroscience

DOI: 10.3389/fnagi.2026.1938752

Authors: Zhixian Gou, Yang Fan, Xiaoping Lei

Institutions: Affiliated Hospital of Southwest Medical University, First Affiliated Hospital of Chengdu Medical College

Language: English

Topic: Neuroinflammation and Neurodegeneration Mechanisms

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801