Abstract
Communication between dying cells and their environment is a critical process that promotes tissue homeostasis during normal cellular turnover, whilst during disease settings, it can contribute to inflammation through the release of intracellular factors. Extracellular vesicles (EVs) are a heterogeneous class of membrane-bound cell-derived structures that can engage in intercellular communication via the trafficking of bioactive molecules between cells and tissues. In addition to the well-described functions of EVs derived from living cells, the ability of dying cells to release EVs capable of mediating functions on target cells or tissues is also of significant interest. In particular, during inflammatory settings such as acute tissue injury, infection and autoimmunity, the EV-mediated transfer of proinflammatory cargo from dying cells is an important process that can elicit profound proinflammatory effects in recipient cells and tissues. Furthermore, the biogenesis of EVs via unique cell-death-associated pathways has also been recently described, highlighting an emerging niche in EV biology. This review outlines the mechanisms and functions of dying-cell-derived EVs and their ability to drive inflammation during various modes of cell death, whilst reflecting on the challenges and knowledge gaps in investigating this subgenre of extracellular vesicles research.
Highlights
Intercellular communication is a ubiquitous process that enables normal developmental, metabolic and immune functions
ApoEVs promoted IL-6, IL-8 and TNFα production in macrophages when coincubated in the presence of IFNa, a proinflammatory cytokine produced by dendritic cells that is detected in circulation at high levels in systemic lupus erythematosus (SLE) patients [44]
These findings collectively indicate that interactions between cargo-bearing Extracellular vesicles (EVs) derived from inflammasome-activated cells and immune cells contribute to an enhanced proinflammatory response
Summary
Intercellular communication is a ubiquitous process that enables normal developmental, metabolic and immune functions. Whilst a short-lived inflammatory response, such as during acute infection, acts to rapidly restore tissue homeostasis through immune cell recruitment and clearance mechanisms, chronic or aberrant inflammation, as seen during cancer, cardiovascular disease and neurodegeneration, can lead to tissue damage through prolonged immune signalling [18]. Direct communication between the released or exposed components of a dying cell and its surrounding tissue is a critical process that can promote efficient clearance of cellular debris and tissue repair during normal cell turnover [22,23,24] but can contribute to inflammation during pathological processes such as infection and autoimmunity [25,26]. It should be noted that during inflammatory conditions, the transport of cargo by EVs derived from dying or inflamed cells can mediate anti-inflammatory and regenerative effects on target cells, described elsewhere [27,28]
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