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ViewAttendees 3

Immunoengineering

Cell and Molecular Immunoengineering

CD200 enhances uptake and degradation of amyloid beta plaques by modulating mitochondria and lysosomes of microglia

Friday, October 10, 2025
9:15 AM - 9:30 AM PDT
Location: Room 24B

Introduction: : Alzheimer and aged microglia shift towards a chronic inflammatory environment. CD200, an immunomodulatory protein that decreases with age, has been shown to decrease inflammatory signaling when added to microglia exogenously. While CD200-based therapies have been investigated for several CNS diseases, its role in modulating microglia energetics and debris clearance is still unknown.

Materials and

Methods: : BV2, a mouse microglia cell line, were cultured with and without soluble CD200 for 48 hours then exposed to fluorescently labelled amyloid-beta fragment 1-42 (Aβ42) that had been previously fibrilized in ammonium hydroxide for one week at 37°C. Uptake was assessed using confocal microscopy and flow cytometry. Mitotracker CMXros Red was used to stain the mitochondria in similarly treated cells, which were then imaged using Airyscan microscopy. Microglia were cultured with CD200 for 24 hours prior to LPS-induced pro-inflammatory polarization for assessment of cytokine production. Lysotracker green was used to quantify the amount of lysosomes present in microglia with and without CD200 or Aβ42, respectively.

Results, Conclusions, and Discussions:: We show the effect of soluble CD200 (sCD200) on enhancing microglial uptake of Aβ after 48 hours of sCD200 pretreatment (Figure 1A,B). We observed rescued mitochondrial network formation and confirmed CD200 functionality as an anti-inflammatory ligand (Figure 1C-E). Lysosomal staining in sCD200-treated microglia prior to amyloid-beta exposure revealed enhanced lysosome activity compared to untreated controls (Figure 1F).

sCD200 induces physical changes in BV2 microglia that involve restructuring of the mitochondrial structure and subsequent energy profile. A decrease in inflammatory cytokine production and shift in lysosomal localization indicate polarization towards an M2-like, or anti-inflammatory, phenotype. However, enhanced uptake which is commonly associated with M1-like polarization was also observed. We show sCD200 can be added exogenously to rejuvenate microglia in vitro by modulating mitochondrial and lysosomal dynamics.

Acknowledgements and/or References (Optional)::