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Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer

Open access
Birge, R B, Boeltz, S, Kumar, S, Carlson, J, Wanderley, J, Calianese, D, Barcinski, M, Brekken, R A, Huang, X, Hutchins, J T, Freimark, B, Empig, C, Mercer, J, Schroit, A J, Schett, G, Herrmann, M·2016·Cell Death & Differentiation

Abstract

Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics.

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Metadata

Authors
Birge, R. B., Boeltz, S., Kumar, S., Carlson, J., Wanderley, J., Calianese, D., Barcinski, M., Brekken, R. A., Huang, X., Hutchins, J. T., Freimark, B., Empig, C., Mercer, J., Schroit, A. J., Schett, G., & Herrmann, M.
Venue
Cell Death & Differentiation
Published
2016-02-26
Volume
23
Issue
6
Pages
962-978
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
OpenAlex
W2285852644
Cited by
725
References
8
FWCI
26.58
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. https://app.cochat.ai/papers/10.1038/cdd.2016.11
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Birge, R. B., Boeltz, S., Kumar, S., Carlson, J., Wanderley, J., Calianese, D., Barcinski, M., Brekken, R. A., Huang, X., Hutchins, J. T., Freimark, B., Empig, C., Mercer, J., Schroit, A. J., Schett, G., & Herrmann, M. (2016). Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. Cell Death & Differentiation. https://doi.org/10.1038/cdd.2016.11

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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