(D-152) CD200 treatment prevents neuroinflammation in murine microglia

Introduction:: CD200 is a broadly expressed immune inhibitory ligand that interacts with the membrane receptor CD200R expressed on myeloid cells. In the central nervous system, CD200 is abundantly found in neurons while CD200R is mainly expressed in microglia. CD200 treatment has been shown to prevent secondary neuronal injury caused by microglia after stroke (Zhao et al., 2019) and to limit macrophage recruitment during atherogenesis (Fernandez-Ruiz, 2021). Previous work from our group has shown that CD200-modified biomaterials increase their phagocytosis, suppress inflammation and reduce immune cell infiltration around biomaterial implants in murine bone-marrow derived macrophages (BMDMs) (Chen et al., J. Mat. Chem B. 2017; Kim et al., Adv. Health. Mat. 2014). In this study, we examined the effects of CD200 on microglia function, in order to explore its potential as a therapeutic to treat neuroinflammation in Alzheimer’s disease (AD).

Materials and Methods:: Murine microglia (BV2) were exposed to CD200 for two hours prior to overnight activation with lipopolysaccharide (LPS). Cytokine secretion was measured using standard ELISA max kits from Biolegend and gene expression was measured by qRT-PCR. Gene expression was normalized to Gapdh. Statistical significance was determined using a two-way ANOVA where p< 0.05.

Results, Conclusions, and Discussions:: We found that CD200 treatment was sufficient to lower IL6 and MCP-1 (or CCL2) secretion in response to LPS stimulation. The exposure of cells to CD200 itself did not affect cytokine secretion. In addition, microglia activated by LPS showed increased expression of inflammatory markers Iba1, Trem2, and Nos2. An increase in migratory promoter Ctgf (or Ccn2), mechanosensitive calcium (Ca2+) channel Piezo1, and calcium entry regulator Trpm7 (Faouzi et al., 2017) are also observed. However, cells treated with CD200 prior to activation expressed lowered levels of Trem2, Trpm7, Ctgf, Nos2, and Piezo1. Together these data suggest microglia are moved towards an inflammatory state as they also prepare for an influx of Ca2+ into the cell when activated by LPS, which is prevented by CD200 treatment prior to activation.

CD200 treatment significantly decreased inflammatory cytokine IL6 and MCP-1, a cytokine involved in cerebral monocyte recruitment and infiltration (D’Mello et al., 2009). Cells treated with CD200 expressed lower levels of genes associated with microglial activation, migration, and calcium infiltration. Current work is focused on CD200 treatment of microglia that have been exposed to toxic aggregates of amyloid-beta (A𝜷), a key characteristic of Alzheimer’s disease (AD).


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Fernández-Ruiz, I. (2021). CD200 is an atheroprotective immune checkpoint. Nature Reviews Cardiology, 18(7), 461–461. https://doi.org/10.1038/s41569-021-00578-5

Zhao, X., Li, J., & Sun, H. (2019). CD200-CD200R interaction: An important regulator after stroke. Frontiers in Neuroscience, 13. https://doi.org/10.3389/fnins.2019.00840