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

First Author  Han MH Year  2012
Journal  J Exp Med Volume  209
Issue  7 Pages  1325-34
PubMed ID  22734047 Mgi Jnum  J:189191
Mgi Id  MGI:5444589 Doi  10.1084/jem.20101974
Citation  Han MH, et al. (2012) Janus-like opposing roles of CD47 in autoimmune brain inflammation in humans and mice. J Exp Med 209(7):1325-34
abstractText  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 alpha (SIRP-alpha). 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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