Fitxers

911607.pdf (12.53 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2025-11-01

Llicència de publicació

cc-by-nc (c) Negro Demontel, Luciana et al, 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/231373

CD300f enables microglial damage sensing, efferocytosis, and apoptotic cell metabolization after brain injury

Títol de la revista

Autors

Director/Tutor

Contribució addicional

ISSN de la revista

Títol del volum

Resum

Microglia, the resident phagocytes of the central nervous system (CNS), continuously survey the parenchyma and its borders, acting as first responders to brain injury. Their ability to detect and react to environmental changes is mediated by a repertoire of surface receptors collectively known as the microglial sensome. Here, we identify the lipid-sensing immunoreceptor CD300f as a key regulator of microglial responses to tissue damage and apoptotic cells. Using intravital two-photon microscopy, we show that CD300f−/− microglia fail to extend processes toward a laser-induced cortical lesion, indicating impaired detection of damage-associated cues. In models of mild traumatic brain injury (mTBI) and intracortical injection of apoptotic cells, CD300f deficiency led to reduced recognition and clearance of dying cells resulting in the accumulation of cellular debris within the parenchyma. At later stages, apoptotic remnants were retained within CD300f−/− microglia in vivo and bone marrow–derived macrophages in vitro, suggesting defective intracellular degradation. Proteomic analysis after a controlled cortical injury (CCI) contusion model revealed widespread dysregulation of autophagy-related and metabolic pathways, consistent with impaired efferocytosis and phagolysosomal processing. In parallel, we observed upregulation of the UDP-degrading ectonucleotidase ENTPD6 protein and downregulation of the microglial purinergic receptor P2ry6 mRNA, indicating a dysfunctional UDP–P2RY6 axis that may underlie impaired damage sensing and phagocytic initiation. Despite greater histological preservation, CD300f−/− mice exhibited worse long-term functional recovery after brain injury. Together, these findings highlight CD300f as a key damage-associated molecular pattern (DAMP) receptor that integrates purinergic signaling, efferocytosis, and metabolic adaptation, highlighting its essential role in coordinating microglial responses to CNS injury.

Recurs relacionat

https://doi.org/10.1016/j.bbi.2025.106105

Matèries

Lesions cerebrals, Citotoxicitat per mediació cel·lular

Matèries (anglès)

Brain damage, Cell-mediated cytotoxicity

Citació

Col·leccions

Articles publicats en revistes (Biomedicina)

Citació

NEGRO DEMONTEL, Luciana, et al. CD300f enables microglial damage sensing, efferocytosis, and apoptotic cell metabolization after brain injury. Brain. Behavior. Vol.  and Immunity, num. 2025, pags. 130. ISSN 0889-1591. [consulted: 24 of October of 2026]. Available at: https://hdl.handle.net/2445/231373

Exportar metadades

JSON - METS

Compartir registre