Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses.
Identifieur interne : 001F25 ( PubMed/Corpus ); précédent : 001F24; suivant : 001F26Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses.
Auteurs : P. Cunin ; C. Beauvillain ; C. Miot ; J-F Augusto ; L. Preisser ; S. Blanchard ; P. Pignon ; M. Scotet ; E. Garo ; I. Fremaux ; A. Chevailler ; J-F Subra ; P. Blanco ; M R Wilson ; P. Jeannin ; Y. DelnesteSource :
- Cell death & disease [ 2041-4889 ] ; 2016.
English descriptors
- KwdEn :
- Animals, Antibodies, Antinuclear (biosynthesis), Antigen Presentation (genetics), Apoptosis (immunology), Autoantigens (genetics), Autoantigens (immunology), Autoimmune Diseases (genetics), Autoimmune Diseases (immunology), Autoimmune Diseases (pathology), Clusterin (genetics), Clusterin (immunology), Coculture Techniques, Cross-Priming (genetics), Dendritic Cells (cytology), Dendritic Cells (immunology), Gene Expression, Humans, Kidney (immunology), Kidney (pathology), Leukocytes, Mononuclear (cytology), Leukocytes, Mononuclear (immunology), Macrophages (cytology), Macrophages (immunology), Mice, Mice, Inbred C57BL, Mice, Knockout, Phagocytosis, Primary Cell Culture, Spleen (immunology), Spleen (pathology), Splenomegaly (genetics), Splenomegaly (immunology), Splenomegaly (pathology).
- MESH :
- chemical , biosynthesis : Antibodies, Antinuclear.
- cytology : Dendritic Cells, Leukocytes, Mononuclear, Macrophages.
- genetics : Antigen Presentation, Autoantigens, Autoimmune Diseases, Clusterin, Cross-Priming, Splenomegaly.
- immunology : Apoptosis, Autoantigens, Autoimmune Diseases, Clusterin, Dendritic Cells, Kidney, Leukocytes, Mononuclear, Macrophages, Spleen, Splenomegaly.
- pathology : Autoimmune Diseases, Kidney, Spleen, Splenomegaly.
- Animals, Coculture Techniques, Gene Expression, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Phagocytosis, Primary Cell Culture.
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.
DOI: 10.1038/cddis.2016.113
PubMed: 27148688
Links to Exploration step
pubmed:27148688Le document en format XML
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<series><title level="j">Cell death & disease</title>
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<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>
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<term>Leukocytes, Mononuclear (cytology)</term>
<term>Leukocytes, Mononuclear (immunology)</term>
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<term>Mice, Inbred C57BL</term>
<term>Mice, Knockout</term>
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<term>Primary Cell Culture</term>
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<term>Splenomegaly (genetics)</term>
<term>Splenomegaly (immunology)</term>
<term>Splenomegaly (pathology)</term>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27148688</PMID>
<DateCreated><Year>2016</Year>
<Month>05</Month>
<Day>06</Day>
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<DateCompleted><Year>2017</Year>
<Month>10</Month>
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<Month>May</Month>
<Day>05</Day>
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<Title>Cell death & disease</Title>
<ISOAbbreviation>Cell Death Dis</ISOAbbreviation>
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<ArticleTitle>Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses.</ArticleTitle>
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</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/cddis.2016.113</ELocationID>
<Abstract><AbstractText>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.</AbstractText>
</Abstract>
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<Initials>P</Initials>
<AffiliationInfo><Affiliation>Université d'Angers, Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Unit 892, Inserm, CHU d'Angers, Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>CNRS, Unit 6299, Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>LabEx IGO "Immuno-Graft-Onco", Angers, France.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Beauvillain</LastName>
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<Initials>C</Initials>
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</AffiliationInfo>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>CNRS, Unit 6299, Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>LabEx IGO "Immuno-Graft-Onco", Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratoire d'Immunologie et d'Allergologie, CHU Angers, Angers, France.</Affiliation>
</AffiliationInfo>
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<AffiliationInfo><Affiliation>LabEx IGO "Immuno-Graft-Onco", Angers, France.</Affiliation>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>CNRS, Unit 6299, Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>LabEx IGO "Immuno-Graft-Onco", Angers, France.</Affiliation>
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<AffiliationInfo><Affiliation>CNRS, Unit 6299, Angers, France.</Affiliation>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>LabEx IGO "Immuno-Graft-Onco", Angers, France.</Affiliation>
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</AffiliationInfo>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>Unit 892, Inserm, CHU d'Angers, Angers, France.</Affiliation>
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</AffiliationInfo>
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<ForeName>M</ForeName>
<Initials>M</Initials>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>Unit 892, Inserm, CHU d'Angers, Angers, France.</Affiliation>
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<AffiliationInfo><Affiliation>CNRS, Unit 6299, Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>LabEx IGO "Immuno-Graft-Onco", Angers, France.</Affiliation>
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<ForeName>E</ForeName>
<Initials>E</Initials>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>CHU Bordeaux, Bordeaux, France.</Affiliation>
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<Initials>Y</Initials>
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</AffiliationInfo>
<AffiliationInfo><Affiliation>CNRS, Unit 6299, Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>LabEx IGO "Immuno-Graft-Onco", Angers, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratoire d'Immunologie et d'Allergologie, CHU Angers, Angers, France.</Affiliation>
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<QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001324" MajorTopicYN="N">Autoantigens</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001327" MajorTopicYN="N">Autoimmune Diseases</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
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<MeshHeading><DescriptorName UI="D051152" MajorTopicYN="N">Clusterin</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
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<MeshHeading><DescriptorName UI="D018920" MajorTopicYN="N">Coculture Techniques</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045142" MajorTopicYN="N">Cross-Priming</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName>
<QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007668" MajorTopicYN="N">Kidney</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
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<MeshHeading><DescriptorName UI="D007963" MajorTopicYN="N">Leukocytes, Mononuclear</DescriptorName>
<QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
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<QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
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<MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010587" MajorTopicYN="N">Phagocytosis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D061251" MajorTopicYN="N">Primary Cell Culture</DescriptorName>
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<MeshHeading><DescriptorName UI="D013154" MajorTopicYN="N">Spleen</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013163" MajorTopicYN="N">Splenomegaly</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
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