Of Tingible Bodies and Starry Skies: Control of Normal and Malignant Tissues Through Apoptotic Cell-Dependent
Stephen J Jenkins1, Christopher D Gregory2
1Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK. stephen.jenkins@ed.ac.uk.
Abstract:
Apoptosis, the original regulated cell death programme, is an established controller of cell populations in all tissues. The hub of the apoptosis machinery, the caspase cascade, mediates the cleavage of hundreds of protein substrates to ultimately effect disabling and dismantling of cells, deleting them in a cell-autonomous fashion that is well understood. Of lesser renown are the intercellular communicative properties of apoptotic cells which, as burgeoning evidence indicates, compound the signalling processes that culminate in the famously speedy, and most commonly non-phlogistic, phagocytic clearance of dying/dead cells and their fragments (efferocytosis) by macrophages and other efferocytes. Here, we discuss more broadly the curious variety of instructive intercellular signals that apoptotic cells can deploy in order to reprogramme their living neighbours, be they close or distant, efferocytes or not. We review the literature, and we consider conceptually the potential of such non-cell-autonomous, apoptotic cell-dependent communication (ACDC) mechanisms to profoundly impact cell populations in health and disease. We illustrate our discourse firstly with the biology of lymphoid germinal centres (GC) and their constituent efferocytic, 'tingible body' macrophages, and secondly with the pathology of malignancies in which counterpart efferocytic, 'starry sky' macrophages feature prominently. In conclusion, we suggest several key avenues in ACDC research.
Insights
Apoptotic cells communicate instructions to neighboring cells, influencing tissue repair and disease. This apoptotic cell-dependent communication (ACDC) impacts cell populations through both efferocytosis and other signaling pathways.
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Apoptosis is a regulated cell death process crucial for tissue homeostasis.
- The caspase cascade is central to apoptosis, dismantling cells autonomously.
- Apoptotic cells also engage in intercellular communication, influencing efferocytosis and neighboring cell behavior.
Purpose of the Study:
- To explore the diverse intercellular signals emitted by apoptotic cells.
- To discuss the concept of apoptotic cell-dependent communication (ACDC).
- To examine the impact of ACDC on cell populations in health and disease.
Main Methods:
- Literature review and conceptual analysis.
- Illustration using examples from lymphoid germinal centers and malignancies.
Main Results:
- Apoptotic cells release instructive signals that reprogram neighboring cells.
- These signals mediate non-cell-autonomous communication (ACDC).
- ACDC plays roles in both normal tissue biology (e.g., germinal centers) and disease (e.g., malignancies).
Conclusions:
- Apoptotic cell-dependent communication (ACDC) is a significant, underappreciated signaling mechanism.
- ACDC profoundly impacts cell populations, affecting health and disease.
- Further research into ACDC mechanisms is warranted.
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