Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin, Daniel; Reis, Edimara S.; Mastellos, Dimitrios C.; Gros, Piet; Lambris, John D.

doi:10.1111/imr.12500

Cited by 484

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Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

Ricklin, Daniel, Reis, Edimara S., Mastellos, Dimitrios C., Gros, Piet, Lambris, John D.·2016·Immunological Reviews

DOI 10.1111/imr.12500PMC PMC5427221

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Abstract

Summary: As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and regulators. Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses. In recent years, it has become evident that nature engages the power of C3 not only to clear pathogens but also for a variety of homeostatic processes ranging from tissue regeneration and synapse pruning to clearing debris and controlling tumor cell progression. At the same time, its central position in immune surveillance makes C3 a target for microbial immune evasion and, if improperly engaged, a trigger point for various clinical conditions. In our review, we look at the versatile roles and evolutionary journey of C3, discuss new insights into the molecular basis for C3 function, provide examples of disease involvement, and summarize the emerging potential of C3 as a therapeutic target.

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miR-132 KD significantly downregulated complement C3 in healthy control iMGs.
“This was further exemplified by the significant downregulation of complement C3, a major component of the complement system, and key player in the immune response [43] (Fig. 1E).”
From microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer’s disease patients (2026) · cites this paper as [43]

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Authors: Ricklin, D., Reis, E. S., Mastellos, D. C., Gros, P., & Lambris, J. D.
Affiliations: Department of Pathology and Laboratory Medicine University of Pennsylvania Philadelphia PA USA
Utrecht University Utrecht The Netherlands
ORCID: Ricklin, Daniel
Gros, Piet
Venue: Immunological Reviews
Publisher: Wiley
Published: 2016-10-26
Volume: 274
Issue: 1
Pages: 33-58
ISSN: 0105-2896
1600-065X
DOI: 10.1111/imr.12500
PMC: PMC5427221
Cited by: 484
References: 7
Language: en
Licence: onlinelibrary.wiley.com/termsAndConditions#am (am, 365 d)
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders: National Institutes of Health (AI068730, AI030040)
National Science Foundation
Seventh Framework Programme (602699)

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Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

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