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 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

68 Citations (Scopus)

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
Externally publishedYes

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Autoimmune Experimental Encephalomyelitis
Encephalitis
Myelin Sheath
Phagocytosis
Multiple Sclerosis
Astrocytes
Paralysis
Proteomics
Immune System
Immunization
Proteins
Down-Regulation
Macrophages
Monoclonal Antibodies
Antigens
Messenger RNA

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Han, M. H., Lundgren, D. H., Jaiswa, S., Chao, M., Graham, K. L., Garris, C. S., ... 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

Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice. / Han, May H.; Lundgren, Deborah H.; Jaiswa, Siddhartha; Chao, Mark; Graham, Kareem L.; Garris, Christopher S.; Axtell, Robert C.; Ho, Peggy P.; Lock, Christopher B.; Woodard, Joslyn I.; Brownell, Sara; Zoudilova, Maria; Hunt, Jack F V; Baranzini, Sergio E.; Butcher, Eugene C.; Raine, Cedric S.; Sobe, Raymond A.; Han, David K.; Weissman, Irving; Steinman, Lawrence.

In: Journal of Experimental Medicine, Vol. 209, No. 7, 02.07.2012, p. 1325-1334.

Research output: Contribution to journalArticle

Han, MH, Lundgren, DH, Jaiswa, S, Chao, M, Graham, KL, Garris, CS, Axtell, RC, Ho, PP, Lock, CB, Woodard, JI, Brownell, S, Zoudilova, M, Hunt, JFV, Baranzini, SE, Butcher, EC, Raine, CS, Sobe, RA, Han, DK, Weissman, I & Steinman, L 2012, 'Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice', Journal of Experimental Medicine, vol. 209, no. 7, pp. 1325-1334. https://doi.org/10.1084/jem.20101974
Han, May H. ; Lundgren, Deborah H. ; Jaiswa, Siddhartha ; Chao, Mark ; Graham, Kareem L. ; Garris, Christopher S. ; Axtell, Robert C. ; Ho, Peggy P. ; Lock, Christopher B. ; Woodard, Joslyn I. ; Brownell, Sara ; Zoudilova, Maria ; Hunt, Jack F V ; Baranzini, Sergio E. ; Butcher, Eugene C. ; Raine, Cedric S. ; Sobe, Raymond A. ; Han, David K. ; Weissman, Irving ; Steinman, Lawrence. / Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 7. pp. 1325-1334.
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