Apoptotic endothelial cells release small extracellular vesicles loaded with immunostimulatory viral-like RNAs
Identifieur interne : 000174 ( Pmc/Curation ); précédent : 000173; suivant : 000175Apoptotic endothelial cells release small extracellular vesicles loaded with immunostimulatory viral-like RNAs
Auteurs : Marie-Pierre Hardy ; Éric Audemard ; Francis Migneault ; Albert Feghaly ; Sylvie Brochu ; Patrick Gendron ; Éric Boilard ; François Major ; Mélanie Dieudé ; Marie-Josée Hébert ; Claude PerreaultSource :
- Scientific Reports [ 2045-2322 ] ; 2019.
Abstract
Endothelial cells have multifaceted interactions with the immune system, both as initiators and targets of immune responses.
Url:
DOI: 10.1038/s41598-019-43591-y
PubMed: 31076589
PubMed Central: 6510763
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Le document en format XML
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<author><name sortKey="Hebert, Marie Josee" sort="Hebert, Marie Josee" uniqKey="Hebert M" first="Marie-Josée" last="Hébert">Marie-Josée Hébert</name>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
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<institution>Research Centre,</institution>
<institution>Centre Hospitalier de l′Université de Montréal (CRCHUM),</institution>
</institution-wrap>
Montreal, QC H2X 0A9 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H2X 0A9 Canada</wicri:noCountry>
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<institution>Université de Montréal,</institution>
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Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
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</author>
<author><name sortKey="Perreault, Claude" sort="Perreault, Claude" uniqKey="Perreault C" first="Claude" last="Perreault">Claude Perreault</name>
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<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Department of Medicine,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Apoptotic endothelial cells release small extracellular vesicles loaded with immunostimulatory viral-like RNAs</title>
<author><name sortKey="Hardy, Marie Pierre" sort="Hardy, Marie Pierre" uniqKey="Hardy M" first="Marie-Pierre" last="Hardy">Marie-Pierre Hardy</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Audemard, Eric" sort="Audemard, Eric" uniqKey="Audemard E" first="Éric" last="Audemard">Éric Audemard</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Migneault, Francis" sort="Migneault, Francis" uniqKey="Migneault F" first="Francis" last="Migneault">Francis Migneault</name>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0743 2111</institution-id>
<institution-id institution-id-type="GRID">grid.410559.c</institution-id>
<institution>Research Centre,</institution>
<institution>Centre Hospitalier de l′Université de Montréal (CRCHUM),</institution>
</institution-wrap>
Montreal, QC H2X 0A9 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H2X 0A9 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Feghaly, Albert" sort="Feghaly, Albert" uniqKey="Feghaly A" first="Albert" last="Feghaly">Albert Feghaly</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Brochu, Sylvie" sort="Brochu, Sylvie" uniqKey="Brochu S" first="Sylvie" last="Brochu">Sylvie Brochu</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gendron, Patrick" sort="Gendron, Patrick" uniqKey="Gendron P" first="Patrick" last="Gendron">Patrick Gendron</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Boilard, Eric" sort="Boilard, Eric" uniqKey="Boilard E" first="Éric" last="Boilard">Éric Boilard</name>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9471 1794</institution-id>
<institution-id institution-id-type="GRID">grid.411081.d</institution-id>
<institution>Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l′Université Laval,</institution>
</institution-wrap>
Québec, Québec Canada</nlm:aff>
<wicri:noCountry code="subfield">Québec Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Major, Francois" sort="Major, Francois" uniqKey="Major F" first="François" last="Major">François Major</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Department of Computer Science and Operations Research,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Department of Biochemistry,</institution>
<institution>Faculty of Medicine, Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Dieude, Melanie" sort="Dieude, Melanie" uniqKey="Dieude M" first="Mélanie" last="Dieudé">Mélanie Dieudé</name>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0743 2111</institution-id>
<institution-id institution-id-type="GRID">grid.410559.c</institution-id>
<institution>Research Centre,</institution>
<institution>Centre Hospitalier de l′Université de Montréal (CRCHUM),</institution>
</institution-wrap>
Montreal, QC H2X 0A9 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H2X 0A9 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Hebert, Marie Josee" sort="Hebert, Marie Josee" uniqKey="Hebert M" first="Marie-Josée" last="Hébert">Marie-Josée Hébert</name>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0743 2111</institution-id>
<institution-id institution-id-type="GRID">grid.410559.c</institution-id>
<institution>Research Centre,</institution>
<institution>Centre Hospitalier de l′Université de Montréal (CRCHUM),</institution>
</institution-wrap>
Montreal, QC H2X 0A9 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H2X 0A9 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Department of Medicine,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Perreault, Claude" sort="Perreault, Claude" uniqKey="Perreault C" first="Claude" last="Perreault">Claude Perreault</name>
<affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff2">Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</nlm:aff>
<wicri:noCountry code="subfield">Alberta T6G 2E1 Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Department of Medicine,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC H3C 3J7 Canada</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">Scientific Reports</title>
<idno type="eISSN">2045-2322</idno>
<imprint><date when="2019">2019</date>
</imprint>
</series>
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<front><div type="abstract" xml:lang="en"><p id="Par1">Endothelial cells have multifaceted interactions with the immune system, both as initiators and targets of immune responses. <italic>In vivo</italic>
, apoptotic endothelial cells release two types of extracellular vesicles upon caspase-3 activation: apoptotic bodies and exosome-like nanovesicles (ApoExos). Only ApoExos are immunogenic: their injection causes inflammation and autoimmunity in mice. Based on deep sequencing of total RNA, we report that apoptotic bodies and ApoExos are loaded with divergent RNA cargos that are not released by healthy endothelial cells. Apoptotic bodies, like endothelial cells, contain mainly ribosomal RNA whereas ApoExos essentially contain non-ribosomal non-coding RNAs. Endogenous retroelements, bearing viral-like features, represented half of total ApoExos RNA content. ApoExos also contained several copies of unedited <italic>Alu</italic>
repeats and large amounts of non-coding RNAs with a demonstrated role in autoimmunity such as U1 RNA and Y RNA. Moreover, ApoExos RNAs had a unique nucleotide composition and secondary structure characterized by strong enrichment in U-rich motifs and unstably folded RNAs. Globally, ApoExos were therefore loaded with RNAs that can stimulate a variety of RIG-I-like receptors and endosomal TLRs. Hence, apoptotic endothelial cells selectively sort in ApoExos a diversified repertoire of immunostimulatory “self RNAs” that are tailor-made for initiation of innate immune responses and autoimmunity.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id>
<journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id>
<journal-title-group><journal-title>Scientific Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2045-2322</issn>
<publisher><publisher-name>Nature Publishing Group UK</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31076589</article-id>
<article-id pub-id-type="pmc">6510763</article-id>
<article-id pub-id-type="publisher-id">43591</article-id>
<article-id pub-id-type="doi">10.1038/s41598-019-43591-y</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Apoptotic endothelial cells release small extracellular vesicles loaded with immunostimulatory viral-like RNAs</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hardy</surname>
<given-names>Marie-Pierre</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-1661-896X</contrib-id>
<name><surname>Audemard</surname>
<given-names>Éric</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Migneault</surname>
<given-names>Francis</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Feghaly</surname>
<given-names>Albert</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brochu</surname>
<given-names>Sylvie</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-9829-2600</contrib-id>
<name><surname>Gendron</surname>
<given-names>Patrick</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Boilard</surname>
<given-names>Éric</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Major</surname>
<given-names>François</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff5">5</xref>
<xref ref-type="aff" rid="Aff6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dieudé</surname>
<given-names>Mélanie</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hébert</surname>
<given-names>Marie-Josée</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
<xref ref-type="aff" rid="Aff7">7</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-9453-7383</contrib-id>
<name><surname>Perreault</surname>
<given-names>Claude</given-names>
</name>
<address><email>claude.perreault@umontreal.ca</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff7">7</xref>
</contrib>
<aff id="Aff1"><label>1</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Institute for Research in Immunology and Cancer,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</aff>
<aff id="Aff2"><label>2</label>
Canadian National Transplant Research Program, Edmonton, Alberta T6G 2E1 Canada</aff>
<aff id="Aff3"><label>3</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0743 2111</institution-id>
<institution-id institution-id-type="GRID">grid.410559.c</institution-id>
<institution>Research Centre,</institution>
<institution>Centre Hospitalier de l′Université de Montréal (CRCHUM),</institution>
</institution-wrap>
Montreal, QC H2X 0A9 Canada</aff>
<aff id="Aff4"><label>4</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9471 1794</institution-id>
<institution-id institution-id-type="GRID">grid.411081.d</institution-id>
<institution>Centre de Recherche du Centre Hospitalier Universitaire de Québec, Faculté de Médecine de l′Université Laval,</institution>
</institution-wrap>
Québec, Québec Canada</aff>
<aff id="Aff5"><label>5</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Department of Computer Science and Operations Research,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</aff>
<aff id="Aff6"><label>6</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Department of Biochemistry,</institution>
<institution>Faculty of Medicine, Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</aff>
<aff id="Aff7"><label>7</label>
<institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2292 3357</institution-id>
<institution-id institution-id-type="GRID">grid.14848.31</institution-id>
<institution>Department of Medicine,</institution>
<institution>Université de Montréal,</institution>
</institution-wrap>
Montreal, QC H3C 3J7 Canada</aff>
</contrib-group>
<pub-date pub-type="epub"><day>10</day>
<month>5</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>10</day>
<month>5</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>9</volume>
<elocation-id>7203</elocation-id>
<history><date date-type="received"><day>13</day>
<month>12</month>
<year>2018</year>
</date>
<date date-type="accepted"><day>26</day>
<month>4</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s) 2019</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
.</license-p>
</license>
</permissions>
<abstract id="Abs1"><p id="Par1">Endothelial cells have multifaceted interactions with the immune system, both as initiators and targets of immune responses. <italic>In vivo</italic>
, apoptotic endothelial cells release two types of extracellular vesicles upon caspase-3 activation: apoptotic bodies and exosome-like nanovesicles (ApoExos). Only ApoExos are immunogenic: their injection causes inflammation and autoimmunity in mice. Based on deep sequencing of total RNA, we report that apoptotic bodies and ApoExos are loaded with divergent RNA cargos that are not released by healthy endothelial cells. Apoptotic bodies, like endothelial cells, contain mainly ribosomal RNA whereas ApoExos essentially contain non-ribosomal non-coding RNAs. Endogenous retroelements, bearing viral-like features, represented half of total ApoExos RNA content. ApoExos also contained several copies of unedited <italic>Alu</italic>
repeats and large amounts of non-coding RNAs with a demonstrated role in autoimmunity such as U1 RNA and Y RNA. Moreover, ApoExos RNAs had a unique nucleotide composition and secondary structure characterized by strong enrichment in U-rich motifs and unstably folded RNAs. Globally, ApoExos were therefore loaded with RNAs that can stimulate a variety of RIG-I-like receptors and endosomal TLRs. Hence, apoptotic endothelial cells selectively sort in ApoExos a diversified repertoire of immunostimulatory “self RNAs” that are tailor-made for initiation of innate immune responses and autoimmunity.</p>
</abstract>
<kwd-group kwd-group-type="npg-subject"><title>Subject terms</title>
<kwd>Transcriptomics</kwd>
<kwd>RNA</kwd>
<kwd>Pattern recognition receptors</kwd>
<kwd>Systems analysis</kwd>
</kwd-group>
<funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/501100000024</institution-id>
<institution>Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)</institution>
</institution-wrap>
</funding-source>
</award-group>
</funding-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2019</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
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