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

Journal Article


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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.

Authors


  •   Cunin, P (external author)
  •   Beauvillain, C (external author)
  •   Miot, C (external author)
  •   Augusto, J-F (external author)
  •   Preisser, L (external author)
  •   Blanchard, S (external author)
  •   Pignon, P (external author)
  •   Scotet, M (external author)
  •   Garo, E (external author)
  •   Fremaux, I (external author)
  •   Chevailler, A (external author)
  •   Subra, J (external author)
  •   Blanco, P (external author)
  •   Mark R Wilson
  •   Jeannin, Pascale (external author)
  •   Delneste, Y (external author)

Publication Date


  • 2016

Citation


  • Cunin, P., Beauvillain, C., Miot, C., Augusto, J., Preisser, L., Blanchard, S., Pignon, P., Scotet, M., Garo, E., Fremaux, I., Chevailler, A., Subra, J., Blanco, P., Wilson, M. R., Jeannin, P. & Delneste, Y. (2016). Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses. Cell Death and Disease, 7 e2215-1-e2215-11.

Scopus Eid


  • 2-s2.0-84966706444

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4805&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3782

Start Page


  • e2215-1

End Page


  • e2215-11

Volume


  • 7

Place Of Publication


  • United Kingdom

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.

Authors


  •   Cunin, P (external author)
  •   Beauvillain, C (external author)
  •   Miot, C (external author)
  •   Augusto, J-F (external author)
  •   Preisser, L (external author)
  •   Blanchard, S (external author)
  •   Pignon, P (external author)
  •   Scotet, M (external author)
  •   Garo, E (external author)
  •   Fremaux, I (external author)
  •   Chevailler, A (external author)
  •   Subra, J (external author)
  •   Blanco, P (external author)
  •   Mark R Wilson
  •   Jeannin, Pascale (external author)
  •   Delneste, Y (external author)

Publication Date


  • 2016

Citation


  • Cunin, P., Beauvillain, C., Miot, C., Augusto, J., Preisser, L., Blanchard, S., Pignon, P., Scotet, M., Garo, E., Fremaux, I., Chevailler, A., Subra, J., Blanco, P., Wilson, M. R., Jeannin, P. & Delneste, Y. (2016). Clusterin facilitates apoptotic cell clearance and prevents apoptotic cell-induced autoimmune responses. Cell Death and Disease, 7 e2215-1-e2215-11.

Scopus Eid


  • 2-s2.0-84966706444

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4805&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3782

Start Page


  • e2215-1

End Page


  • e2215-11

Volume


  • 7

Place Of Publication


  • United Kingdom