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Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses

Identifieur interne : 002218 ( Main/Curation ); précédent : 002217; suivant : 002219

Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses

Auteurs : P. Cunin [France] ; C. Beauvillain [France] ; C. Miot [France] ; J-F Augusto [France] ; L. Preisser [France] ; S. Blanchard [France] ; P. Pignon [France] ; M. Scotet [France] ; E. Garo [France] ; I. Fremaux [France] ; A. Chevailler [France] ; J-F Subra [France] ; P. Blanco [France] ; M R Wilson [Australie] ; P. Jeannin [France] ; Y. Delneste [France]

Source :

RBID : PMC:4917652

Descripteurs français

English descriptors

Abstract

Clusterin (Clu), an extracellular chaperone, exhibits characteristics of soluble innate immunity receptors, as assessed by its ability to bind some bacteria strains. In this study, we report that Clu also binds specifically to late apoptotic cells but not to live, early apoptotic, or necrotic cells. Histones, which accumulate on blebs during the apoptotic process, represent privileged Clu-binding motifs at the surface of late apoptotic cells. As a consequence, Clu potentiates, both in vitro and in vivo, the phagocytosis of late apoptotic cells by macrophages. Moreover, the increased phagocytosis of late apoptotic cells induced by Clu favors the presentation and cross-presentation of apoptotic cell-associated antigens. Finally, we observed that, in a model of apoptotic cell-induced autoimmunity, and relative to control mice, Clu−/− mice develop symptoms of autoimmunity, including the generation of anti-dsDNA antibodies, deposition of immunoglobulins and complement components within kidneys, and splenomegaly. These results identify Clu as a new molecule partner involved in apoptotic cell efferocytosis and suggest a protective role for Clu in inflammation and autoimmune diseases.


Url:
DOI: 10.1038/cddis.2016.113
PubMed: 27148688
PubMed Central: 4917652

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PMC:4917652

Le document en format XML

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<name sortKey="Pignon, P" sort="Pignon, P" uniqKey="Pignon P" first="P" last="Pignon">P. Pignon</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Scotet, M" sort="Scotet, M" uniqKey="Scotet M" first="M" last="Scotet">M. Scotet</name>
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<name sortKey="Garo, E" sort="Garo, E" uniqKey="Garo E" first="E" last="Garo">E. Garo</name>
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<name sortKey="Fremaux, I" sort="Fremaux, I" uniqKey="Fremaux I" first="I" last="Fremaux">I. Fremaux</name>
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<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<name sortKey="Blanco, P" sort="Blanco, P" uniqKey="Blanco P" first="P" last="Blanco">P. Blanco</name>
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<institution>Université Victor Segalen</institution>
, Bordeaux,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>CNRS Unit 5164</institution>
, Bordeaux,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>CHU Bordeaux</institution>
, Bordeaux,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="Wilson, M R" sort="Wilson, M R" uniqKey="Wilson M" first="M R" last="Wilson">M R Wilson</name>
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<institution>School of Biological Sciences, Illawarra Health and Medical Research Institute, University of Wollongong</institution>
, Wollongong, New South Wales,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
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<name sortKey="Jeannin, P" sort="Jeannin, P" uniqKey="Jeannin P" first="P" last="Jeannin">P. Jeannin</name>
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<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Laboratoire d'Immunologie et d'Allergologie, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Delneste, Y" sort="Delneste, Y" uniqKey="Delneste Y" first="Y" last="Delneste">Y. Delneste</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Laboratoire d'Immunologie et d'Allergologie, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PMC</idno>
<idno type="pmid">27148688</idno>
<idno type="pmc">4917652</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917652</idno>
<idno type="RBID">PMC:4917652</idno>
<idno type="doi">10.1038/cddis.2016.113</idno>
<date when="2016">2016</date>
<idno type="wicri:Area/Pmc/Corpus">000714</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000714</idno>
<idno type="wicri:Area/Pmc/Curation">000713</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000713</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000A69</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000A69</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">001F25</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001F25</idno>
<idno type="wicri:Area/PubMed/Curation">001F01</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001F01</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001F01</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001F01</idno>
<idno type="wicri:Area/Ncbi/Merge">003512</idno>
<idno type="wicri:Area/Ncbi/Curation">003512</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">003512</idno>
<idno type="wicri:Area/Main/Merge">002217</idno>
<idno type="wicri:Area/Main/Curation">002218</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en" level="a" type="main">Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses</title>
<author>
<name sortKey="Cunin, P" sort="Cunin, P" uniqKey="Cunin P" first="P" last="Cunin">P. Cunin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Beauvillain, C" sort="Beauvillain, C" uniqKey="Beauvillain C" first="C" last="Beauvillain">C. Beauvillain</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Laboratoire d'Immunologie et d'Allergologie, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Miot, C" sort="Miot, C" uniqKey="Miot C" first="C" last="Miot">C. Miot</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Augusto, J F" sort="Augusto, J F" uniqKey="Augusto J" first="J-F" last="Augusto">J-F Augusto</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<institution>Service de Néphrologie-Dialyse-Transplantation, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Preisser, L" sort="Preisser, L" uniqKey="Preisser L" first="L" last="Preisser">L. Preisser</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Blanchard, S" sort="Blanchard, S" uniqKey="Blanchard S" first="S" last="Blanchard">S. Blanchard</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Laboratoire d'Immunologie et d'Allergologie, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Pignon, P" sort="Pignon, P" uniqKey="Pignon P" first="P" last="Pignon">P. Pignon</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Scotet, M" sort="Scotet, M" uniqKey="Scotet M" first="M" last="Scotet">M. Scotet</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Garo, E" sort="Garo, E" uniqKey="Garo E" first="E" last="Garo">E. Garo</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Fremaux, I" sort="Fremaux, I" uniqKey="Fremaux I" first="I" last="Fremaux">I. Fremaux</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Chevailler, A" sort="Chevailler, A" uniqKey="Chevailler A" first="A" last="Chevailler">A. Chevailler</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Laboratoire d'Immunologie et d'Allergologie, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Subra, J F" sort="Subra, J F" uniqKey="Subra J" first="J-F" last="Subra">J-F Subra</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<institution>Service de Néphrologie-Dialyse-Transplantation, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Blanco, P" sort="Blanco, P" uniqKey="Blanco P" first="P" last="Blanco">P. Blanco</name>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<institution>Université Victor Segalen</institution>
, Bordeaux,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff8">
<institution>CNRS Unit 5164</institution>
, Bordeaux,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff9">
<institution>CHU Bordeaux</institution>
, Bordeaux,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Wilson, M R" sort="Wilson, M R" uniqKey="Wilson M" first="M R" last="Wilson">M R Wilson</name>
<affiliation wicri:level="1">
<nlm:aff id="aff10">
<institution>School of Biological Sciences, Illawarra Health and Medical Research Institute, University of Wollongong</institution>
, Wollongong, New South Wales,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Jeannin, P" sort="Jeannin, P" uniqKey="Jeannin P" first="P" last="Jeannin">P. Jeannin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Laboratoire d'Immunologie et d'Allergologie, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Delneste, Y" sort="Delneste, Y" uniqKey="Delneste Y" first="Y" last="Delneste">Y. Delneste</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Université d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff2">
<institution>Unit 892, Inserm, CHU d'Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<institution>CNRS, Unit 6299</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<institution>LabEx IGO "Immuno-Graft-Onco"</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff5">
<institution>Laboratoire d'Immunologie et d'Allergologie, CHU Angers</institution>
, Angers,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Cell Death & Disease</title>
<idno type="eISSN">2041-4889</idno>
<imprint>
<date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Antibodies, Antinuclear (biosynthesis)</term>
<term>Antigen Presentation (genetics)</term>
<term>Apoptosis (immunology)</term>
<term>Autoantigens (genetics)</term>
<term>Autoantigens (immunology)</term>
<term>Autoimmune Diseases (genetics)</term>
<term>Autoimmune Diseases (immunology)</term>
<term>Autoimmune Diseases (pathology)</term>
<term>Clusterin (genetics)</term>
<term>Clusterin (immunology)</term>
<term>Coculture Techniques</term>
<term>Cross-Priming (genetics)</term>
<term>Dendritic Cells (cytology)</term>
<term>Dendritic Cells (immunology)</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Kidney (immunology)</term>
<term>Kidney (pathology)</term>
<term>Leukocytes, Mononuclear (cytology)</term>
<term>Leukocytes, Mononuclear (immunology)</term>
<term>Macrophages (cytology)</term>
<term>Macrophages (immunology)</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Phagocytosis</term>
<term>Primary Cell Culture</term>
<term>Spleen (immunology)</term>
<term>Spleen (pathology)</term>
<term>Splenomegaly (genetics)</term>
<term>Splenomegaly (immunology)</term>
<term>Splenomegaly (pathology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Agranulocytes (cytologie)</term>
<term>Agranulocytes (immunologie)</term>
<term>Animaux</term>
<term>Anticorps antinucléaires (biosynthèse)</term>
<term>Apoptose (immunologie)</term>
<term>Autoantigènes (génétique)</term>
<term>Autoantigènes (immunologie)</term>
<term>Cellules dendritiques (cytologie)</term>
<term>Cellules dendritiques (immunologie)</term>
<term>Clusterine (génétique)</term>
<term>Clusterine (immunologie)</term>
<term>Cross-priming (génétique)</term>
<term>Culture primaire de cellules</term>
<term>Expression des gènes</term>
<term>Humains</term>
<term>Macrophages (cytologie)</term>
<term>Macrophages (immunologie)</term>
<term>Maladies auto-immunes (anatomopathologie)</term>
<term>Maladies auto-immunes (génétique)</term>
<term>Maladies auto-immunes (immunologie)</term>
<term>Phagocytose</term>
<term>Présentation d'antigène (génétique)</term>
<term>Rate (anatomopathologie)</term>
<term>Rate (immunologie)</term>
<term>Rein (anatomopathologie)</term>
<term>Rein (immunologie)</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Splénomégalie (anatomopathologie)</term>
<term>Splénomégalie (génétique)</term>
<term>Splénomégalie (immunologie)</term>
<term>Techniques de coculture</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en">
<term>Antibodies, Antinuclear</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr">
<term>Maladies auto-immunes</term>
<term>Rate</term>
<term>Rein</term>
<term>Splénomégalie</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr">
<term>Anticorps antinucléaires</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr">
<term>Agranulocytes</term>
<term>Cellules dendritiques</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en">
<term>Dendritic Cells</term>
<term>Leukocytes, Mononuclear</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Antigen Presentation</term>
<term>Autoantigens</term>
<term>Autoimmune Diseases</term>
<term>Clusterin</term>
<term>Cross-Priming</term>
<term>Splenomegaly</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Autoantigènes</term>
<term>Clusterine</term>
<term>Cross-priming</term>
<term>Maladies auto-immunes</term>
<term>Présentation d'antigène</term>
<term>Splénomégalie</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr">
<term>Agranulocytes</term>
<term>Apoptose</term>
<term>Autoantigènes</term>
<term>Cellules dendritiques</term>
<term>Clusterine</term>
<term>Macrophages</term>
<term>Maladies auto-immunes</term>
<term>Rate</term>
<term>Rein</term>
<term>Splénomégalie</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>Apoptosis</term>
<term>Autoantigens</term>
<term>Autoimmune Diseases</term>
<term>Clusterin</term>
<term>Dendritic Cells</term>
<term>Kidney</term>
<term>Leukocytes, Mononuclear</term>
<term>Macrophages</term>
<term>Spleen</term>
<term>Splenomegaly</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en">
<term>Autoimmune Diseases</term>
<term>Kidney</term>
<term>Spleen</term>
<term>Splenomegaly</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Coculture Techniques</term>
<term>Gene Expression</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
<term>Phagocytosis</term>
<term>Primary Cell Culture</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Culture primaire de cellules</term>
<term>Expression des gènes</term>
<term>Humains</term>
<term>Phagocytose</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Souris knockout</term>
<term>Techniques de coculture</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>Clusterin (Clu), an extracellular chaperone, exhibits characteristics of soluble innate immunity receptors, as assessed by its ability to bind some bacteria strains. In this study, we report that Clu also binds specifically to late apoptotic cells but not to live, early apoptotic, or necrotic cells. Histones, which accumulate on blebs during the apoptotic process, represent privileged Clu-binding motifs at the surface of late apoptotic cells. As a consequence, Clu potentiates, both
<italic>in vitro</italic>
and
<italic>in vivo</italic>
, the phagocytosis of late apoptotic cells by macrophages. Moreover, the increased phagocytosis of late apoptotic cells induced by Clu favors the presentation and cross-presentation of apoptotic cell-associated antigens. Finally, we observed that, in a model of apoptotic cell-induced autoimmunity, and relative to control mice, Clu
<sup>−/−</sup>
mice develop symptoms of autoimmunity, including the generation of anti-dsDNA antibodies, deposition of immunoglobulins and complement components within kidneys, and splenomegaly. These results identify Clu as a new molecule partner involved in apoptotic cell efferocytosis and suggest a protective role for Clu in inflammation and autoimmune diseases.</p>
</div>
</front>
<back>
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