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Cited by 157Phagocytosis and Immune RegulationMultiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration Mechanisms

Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice

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Han, May H., Lundgren, Deborah H., Jaiswal, Siddhartha, Chao, Mark, Graham, Kareem L., Garris, Christopher S., Axtell, Robert C., Ho, Peggy P. +12 more·2012·Journal of Experimental Medicine
DOI 10.1084/jem.20101974PMC PMC3405500
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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.

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  • A significant decrease in BIN1 expression was observed in microarray analysis of multiple sclerosis brain lesions compared with control brain samples.

    “a significant decrease in BIN1 expression was observed in microarray analysis of multiple sclerosis brain lesions in comparison with control brain samples (GEO DataSet GDS4218) [51].”

    From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [51]

    The Results section describes microarray analysis of MS brain lesions, but the passages found do not report BIN1 expression or a significant decrease relative to controls. Searching the indexed paper for BIN1 and GDS4218 found no supporting passage; Materials and Methods instead lists the paper’s microarray data under GSE38010. No page numbers are available in our copy. (LLM, conf=0.73)

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Authors
Han, M. H., Lundgren, D. H., Jaiswal, S., Chao, M., Graham, K. L., Garris, C. S., Axtell, R. C., Ho, P. P., Lock, C. B., Woodard, J. I., Brownell, S. E., Zoudilova, M., Hunt, J. F. V., Baranzini, S. E., Butcher, E. C., Raine, C. S., Sobel, R. A., Han, D. K., Weissman, I., & Steinman, L.
Affiliations
  • Institute for Stem Cell Biology and Regenerative Medicine (IN)
  • UConn Health (US)
  • University of California, San Francisco (US)
  • Albert Einstein College of Medicine (US)
Corresponding author
  • Han, May H.
  • Steinman, Lawrence
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2012-06-25
Volume
209
Issue
7
Pages
1325-1334
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20101974
PMC
PMC3405500
OpenAlex
W2140933978
Cited by
157
References
3
Citations by year
2026: 7 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 14 · 2021: 14 · 2020: 14 · 2019: 16 · 2018: 17 · 2017: 12 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 8 · 2012: 2
FWCI
4.20
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Cancer Institute (T32CA009302)
  • National Institute of Allergy and Infectious Diseases (T32AI007290)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
CD47, multiple sclerosis, experimental autoimmune encephalomyelitis, autoimmune neuroinflammation, SIRPα, myelin phagocytosis, immune cell activation, reactive astrocytes, foam cells
MeSH terms
Animals, Antigen-Presenting Cells, Astrocytes, Autoimmune Diseases, Encephalitis, Encephalomyelitis, Autoimmune, Experimental, Flow Cytometry, Foam Cells, Humans, Immunohistochemistry, Mice, Inbred C57BL, Multiple Sclerosis, Myelin Sheath, T-Lymphocytes, Down-Regulation, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Proteomics, Mice, CD47 Antigen, Transcriptome, Disease Resistance

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