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Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses
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....
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917652/ https://www.ncbi.nlm.nih.gov/pubmed/27148688 http://dx.doi.org/10.1038/cddis.2016.113 |
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author | Cunin, P Beauvillain, C Miot, C Augusto, J-F Preisser, L Blanchard, S Pignon, P Scotet, M Garo, E Fremaux, I Chevailler, A Subra, J-F Blanco, P Wilson, M R Jeannin, P Delneste, Y |
author_facet | Cunin, P Beauvillain, C Miot, C Augusto, J-F Preisser, L Blanchard, S Pignon, P Scotet, M Garo, E Fremaux, I Chevailler, A Subra, J-F Blanco, P Wilson, M R Jeannin, P Delneste, Y |
author_sort | Cunin, P |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4917652 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49176522016-07-07 Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses Cunin, P Beauvillain, C Miot, C Augusto, J-F Preisser, L Blanchard, S Pignon, P Scotet, M Garo, E Fremaux, I Chevailler, A Subra, J-F Blanco, P Wilson, M R Jeannin, P Delneste, Y Cell Death Dis Original Article 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. Nature Publishing Group 2016-05 2016-05-05 /pmc/articles/PMC4917652/ /pubmed/27148688 http://dx.doi.org/10.1038/cddis.2016.113 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Cunin, P Beauvillain, C Miot, C Augusto, J-F Preisser, L Blanchard, S Pignon, P Scotet, M Garo, E Fremaux, I Chevailler, A Subra, J-F Blanco, P Wilson, M R Jeannin, P Delneste, Y Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses |
title | Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses |
title_full | Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses |
title_fullStr | Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses |
title_full_unstemmed | Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses |
title_short | Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses |
title_sort | clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917652/ https://www.ncbi.nlm.nih.gov/pubmed/27148688 http://dx.doi.org/10.1038/cddis.2016.113 |
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