The dead cell diet: Efferocytosis as a determinant of macrophage cellular state
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The dead cell diet: Efferocytosis as a determinant of macrophage cellular state

Machlan Sawden
,
Marc H. Wadsworth
,
Thomas Fabre
*
,
Cynthia Lebeaupin
*
*Correspondence to: Thomas Fabre, Pfizer Inc. Cambridge, MA 02139, USA. E-mail: Thomas.Fabre@pfizer.com
Cynthia Lebeaupin, Pfizer Inc. Cambridge, MA 02139, USA. E-mail: Cynthia.Lebeaupin@pfizer.com
Myeloid Cells. 2026;1:202610. 10.70401/mc.2026.0005
Received: May 02, 2026Accepted: June 24, 2026Published: June 24, 2026
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This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Macrophage efferocytosis is the phagocytic clearance of apoptotic cells. This fundamental process governs tissue homeostasis, immune tolerance, and the resolution of inflammation. Immune and metabolic reprogramming are essential to sustain efferocytic capacity. Maladaptive efferocytosis is mostly considered “incomplete or nonfunctional” in chronic diseases, but can also be characterized by misinterpreted, mistimed, or mischaracterized efferocytic events. A central barrier to progress has been the inability to define efferocytic macrophages as functional entities, rather than transient, poorly resolved states obscured by technical and conceptual limitations. Here, we review efferocytosis across health and disease by linking apoptotic cargo identity, macrophage processing capacity, and inflammatory and metabolic constraints to efferocytic throughput. We further highlight the technical challenges that cause bona fide efferocytic states to be misclassified or excluded in high‑dimensional datasets. Applying an updated framework acknowledging complexity of macrophage efferocytosis will ultimately enable the development of novel therapeutic strategies.

Keywords

Macrophages, apoptosis, efferocytosis, phagocytosis, homeostasis, inflammation, metabolism, multiomics/transcriptomics

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Sawden M, Wadsworth MH, Fabre T, Lebeaupin C. The dead cell diet: Efferocytosis as a determinant of macrophage cellular state. Myeloid Cells. 2026;1:202610. https://doi.org/10.70401/mc.2026.0005

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