Uncoupling complement C1s activation from C1q binding in apoptotic cell phagocytosis and immunosuppressive capacity

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Lucrezia ColonnaKeith B Elkon

Abstract

Complement activation contributes to inflammation in many diseases, yet it also supports physiologic apoptotic cells (AC) clearance and its downstream immunosuppressive effects. The roles of individual complement components in AC phagocytosis have been difficult to dissect with artificially depleted sera. Using human in vitro systems and the novel antibody complement C1s inhibitor TNT003, we uncoupled the role of the enzymatic activation of the classical pathway from the opsonizing role of C1q in mediating a) the phagocytosis of early and late AC, and b) the immunosuppressive capacity of early AC. We found that C1s inhibition had a small impact on the physiologic clearance of early AC, leaving their immunosuppressive properties entirely unaffected, while mainly inhibiting the phagocytosis of late apoptotic/secondary necrotic cells. Our data suggest that C1s inhibition may represent a valuable therapeutic strategy to control classical pathway activation without causing significant AC accumulation in diseases without defects in AC phagocytosis.

References

Jan 1, 1994·Springer Seminars in Immunopathology·B P Morgan, S Meri
Dec 22, 1998·The Journal of Experimental Medicine·D MevorachK B Elkon
Jul 13, 2002·European Journal of Immunology·Alma J NautaAnja Roos
Oct 31, 2003·Essays in Biochemistry·Aimee M deCathelineau, Peter M Henson
Mar 23, 2004·Annual Review of Immunology·Anthony P MandersonMark J Walport
Jun 23, 2004·Trends in Immunology·Christine GaboriaudGérard J Arlaud
Aug 10, 2005·The Journal of Biological Chemistry·Kristina ElwardPhilippe Gasque
Apr 6, 2006·Trends in Immunology·Peter M Henson, David A Hume
Apr 28, 2006·Journal of Leukocyte Biology·Shyra J GardaiPeter M Henson
Mar 10, 2010·Cell·Shigekazu NagataKohki Kawane
Jun 30, 2010·The Journal of Cell Biology·Michael R Elliott, Kodi S Ravichandran
Aug 20, 2010·Nature Immunology·Daniel RicklinJohn D Lambris
Jun 21, 2012·Journal of Leukocyte Biology·Manuel D GalvanSuzanne S Bohlson
Aug 11, 2012·The Journal of Biological Chemistry·Myriam MartinAnna M Blom
Aug 28, 2012·Immunity·Michael C Carroll, David E Isenman
Oct 23, 2012·Nature Immunology·Gaëlle Le FriecClaudia Kemper
Oct 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Myoungsun SonBetty Diamond
Jul 31, 2013·Nature Immunology·Zaida G Ramirez-OrtizTerry K Means
Feb 1, 2014·Nature Reviews. Immunology·Ivan K H PoonKodi S Ravichandran
May 31, 2014·Cell Death & Disease·Y Y LiangR Oehler
Jul 18, 2014·Clinical and Vaccine Immunology : CVI·Allison M BradyMoon H Nahm
Jul 19, 2014·Current Opinion in Rheumatology·Lucrezia ColonnaKeith B Elkon
Dec 3, 2014·European Journal of Immunology·Pirkka T PekkarinenT Petteri Arstila
Apr 24, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·K A ThomasE F Reed
Jun 16, 2015·Frontiers in Immunology·Nicolas S MerleLubka T Roumenina

❮ Previous
Next ❯

Citations

Oct 27, 2016·Immunological Reviews·Myriam Martin, Anna M Blom
Mar 20, 2018·Genes and Immunity·Kozue Uchio-YamadaNoboru Manabe
Feb 6, 2018·Annual Review of Immunology·Shigekazu Nagata
Aug 31, 2018·International Immunology·Mahiru Kawano, Shigekazu Nagata
Jan 13, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pavel A NikitinSandip Panicker
Jun 14, 2017·The Journal of Experimental Medicine·Christian LoodKeith B Elkon
Jan 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrea J Tenner
Sep 4, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brandon L GarciaBrian V Geisbrecht
Nov 13, 2020·Journal of Neuroinflammation·Jeffrey M HarderGareth R Howell
Apr 8, 2021·The New England Journal of Medicine·Alexander RöthSigbjørn Berentsen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.

Related Papers

Biochemistry
M A Calcott, H J Müller-Eberhard
Proceedings of the European Dialysis and Transplant Association
N J DoddM J Weston
The Journal of Immunology : Official Journal of the American Association of Immunologists
H R KnobelH Isliker
© 2022 Meta ULC. All rights reserved