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

May H. Han, Deborah H. Lundgren, Siddhartha Jaiswa, Mark Chao, Kareem L. Graham, Christopher S. Garris, Robert C. Axtell, Peggy P. Ho, Christopher B. Lock, Joslyn I. Woodard, Sara E. Brownell, Maria Zoudilova, Jack F.V. Hunt, Sergio E. Baranzini, Eugene C. Butcher, Cedric S. Raine, Raymond A. Sobe, David K. Han, Irving Weissman, Lawrence Steinman

Research output: Contribution to journalArticle

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1325-1334
Number of pages10
JournalJournal of Experimental Medicine
Volume209
Issue number7
DOIs
StatePublished - Jul 2 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice'. Together they form a unique fingerprint.

  • Cite this

    Han, M. H., Lundgren, D. H., Jaiswa, 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., Sobe, R. A., Han, D. K., Weissman, I., & Steinman, L. (2012). Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice. Journal of Experimental Medicine, 209(7), 1325-1334. https://doi.org/10.1084/jem.20101974