Related Experiment Video
Updated: May 21, 2026
Targeted Knockdown of Genes in the Choroid Plexus
Published on: June 16, 2023
Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice
May H Han1, Deborah H Lundgren, Siddhartha Jaiswal
1Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. mayhan@stanford.edu
Abstract:
Comparison of transcriptomic and proteomic data from pathologically similar multiple sclerosis (MS) lesions reveals down-regulation of CD47 at the messenger RNA level and low abundance at the protein level. Immunohistochemical studies demonstrate that CD47 is expressed in normal myelin and in foamy macrophages and reactive astrocytes within active MS lesions. We demonstrate that CD47(-/-) mice are refractory to experimental autoimmune encephalomyelitis (EAE), primarily as the result of failure of immune cell activation after immunization with myelin antigen. In contrast, blocking with a monoclonal antibody against CD47 in mice at the peak of paralysis worsens EAE severity and enhances immune activation in the peripheral immune system. In vitro assays demonstrate that blocking CD47 also promotes phagocytosis of myelin and that this effect is dependent on signal regulatory protein α (SIRP-α). Immune regulation and phagocytosis are mechanisms for CD47 signaling in autoimmune neuroinflammation. Depending on the cell type, location, and disease stage, CD47 has Janus-like roles, with opposing effects on EAE pathogenesis.
Insights
CD47, a protein found in multiple sclerosis (MS) lesions, plays a dual role in autoimmune neuroinflammation. Its absence protects against experimental autoimmune encephalomyelitis (EAE), while blocking it worsens EAE and promotes myelin phagocytosis.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Cellular Biology
Background:
- Multiple sclerosis (MS) involves complex immune responses and neuroinflammation.
- CD47, a transmembrane protein, is implicated in immune cell regulation.
- Understanding CD47's role in MS pathogenesis is crucial for developing new therapies.
Purpose of the Study:
- To investigate the role of CD47 in the pathogenesis of multiple sclerosis (MS).
- To explore the dual functions of CD47 in autoimmune neuroinflammation and experimental autoimmune encephalomyelitis (EAE).
Main Methods:
- Comparative analysis of transcriptomic and proteomic data from MS lesions.
- Immunohistochemical staining to determine CD47 expression patterns.
- Utilizing CD47 knockout mice and monoclonal antibody blockade in EAE models.
- In vitro phagocytosis assays involving myelin and signal regulatory protein α (SIRP-α).
Main Results:
- CD47 is downregulated at mRNA and protein levels in MS lesions.
- CD47 knockout mice are resistant to EAE due to impaired immune cell activation.
- Blocking CD47 exacerbates EAE and enhances peripheral immune activation.
- CD47 blockade promotes myelin phagocytosis in a SIRP-α-dependent manner.
Conclusions:
- CD47 exhibits Janus-like roles in autoimmune neuroinflammation, with context-dependent effects on EAE.
- CD47 signaling influences immune regulation and phagocytosis in the central nervous system.
- Targeting CD47 may offer therapeutic potential for MS, but requires careful consideration of its opposing functions.
More Related Videos
08:47Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
10:50Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019