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Published on: October 27, 2014
WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature
Ivan B Lobov1, Sujata Rao, Thomas J Carroll
1Division of Developmental Biology, The Children's Hospital Research Foundation and Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio 45229, USA.
Abstract:
Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells. Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions--including cell death--in adjacent cells, and raise the possibility that they do so in many different cellular contexts.
Insights
Macrophages trigger programmed cell death in neighboring cells by activating the WNT pathway. This study reveals macrophage WNT7b signaling is crucial for vascular endothelial cell death during eye development in mice.
Area of Science:
- Immunology
- Developmental Biology
- Cell Signaling
Background:
- Macrophages are key immune cells involved in inflammatory and immune responses.
- Their role includes recognizing and engulfing apoptotic cells.
- The mechanisms by which macrophages influence target cell fate are not fully understood.
Purpose of the Study:
- To investigate whether macrophages can actively induce cell death in adjacent cells.
- To identify the signaling pathways involved in macrophage-mediated cell death.
- To explore the role of WNT signaling in this process.
Main Methods:
- Utilized mouse models to study macrophage-target cell interactions.
- Investigated the activation of the canonical WNT pathway.
- Focused on programmed cell death in vascular endothelial cells during eye development.
Main Results:
- Macrophages were shown to initiate a programmed cell-death pathway in target cells.
- This process involves the activation of the canonical WNT pathway.
- Macrophage-secreted WNT7b acts as a paracrine signal essential for WNT pathway activation and programmed cell death in developing ocular vascular endothelial cells.
Conclusions:
- Macrophages can actively induce cell death in adjacent cells through WNT ligand signaling.
- WNT7b secreted by macrophages plays a critical role in regulating cell-fate decisions, specifically cell death.
- This mechanism may be broadly applicable in various cellular contexts during development and disease.
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