title: CD47-dependent immunomodulatory and angiogenic activities of extracellular vesicles produced by T cells.
abstract: Intercellular communication is critical for integrating complex signals in multicellular eukaryotes. Vascular endothelial cells and T lymphocytes closely interact during the recirculation and trans-endothelial migration of T cells. In addition to direct cell-cell contact, we show that T cell derived extracellular vesicles can interact with endothelial cells and modulate their cellular functions. Thrombospondin-1 and its receptor CD47 are expressed on exosomes/ectosomes derived from T cells, and these extracellular vesicles are internalized and modulate signaling in both T cells and endothelial cells. Extracellular vesicles released from cells expressing or lacking CD47 differentially regulate activation of T cells induced by engaging the T cell receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial cell responses to vascular endothelial growth factor and tube formation in a CD47-dependent manner. Uptake of T cell derived extracellular vesicles by recipient endothelial cells globally alters gene expression in a CD47-dependent manner. CD47 also regulates the mRNA content of extracellular vesicles in a manner consistent with some of the resulting alterations in target endothelial cell gene expression. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly regulates intercellular communication mediated by the transfer of extracellular vesicles between vascular cells.
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20982, USA.
authors.forename: Sukhbir
authors.initials: S
authors.lastname: Kaur
authors.affiliation: Inflammation Biology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20982, USA.
authors.forename: Satya P
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
authors.affiliation: Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Histopathology Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mones S
authors.initials: MS
authors.lastname: Abu-Asab
authors.affiliation: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20982, USA. Electronic address: droberts@helix.nih.gov.
authors.forename: David D
authors.initials: DD
authors.lastname: Roberts
mesh_terms: D000704:Analysis of Variance; D043924:Angiogenesis Modulating Agents / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D015153:Blotting, Western; D051928:CD47 Antigen / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology*; D047468:Immunoprecipitation; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*
chemical_list: D043924:Angiogenesis Modulating Agents; D051928:CD47 Antigen; C497894:CD47 protein, human; D017931:DNA Primers; D007155:Immunologic Factors; D019700:Thrombospondin 1
keywords: CD47; Extracellular vesicles; Intercellular communication; Thrombospondin-1