Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells

Abstract

Chronic inflammation involving both innate and adaptive immune cells is implicated in the pathogenesis of asthma. Intercellular communication is essential for driving and resolving inflammatory responses in asthma. Emerging studies suggest that extracellular vesicles (EVs) including exosomes facilitate this process. In this report, we have used a range of approaches to show that EVs contain markers of mitochondria derived from donor cells which are capable of sustaining a membrane potential. Further, we propose that these participate in intercellular communication within the airways of human subjects with asthma. Bronchoalveolar lavage fluid of both healthy volunteers and asthmatics contain EVs with encapsulated mitochondria; however, the % HLA-DR+ EVs containing mitochondria and the levels of mitochondrial DNA within EVs were significantly higher in asthmatics. Furthermore, mitochondria are present in exosomes derived from the pro-inflammatory HLA-DR+ subsets of airway myeloid-derived regulatory cells (MDRCs), which are known regulators of T cell responses in asthma. Exosomes tagged with MitoTracker Green, or derived from MDRCs transduced with CellLight Mitochondrial GFP were found in recipient peripheral T cells using a co-culture system, supporting direct exosome-mediated cell-cell transfer. Importantly, exosomally transferred mitochondria co-localize with the mitochondrial network and generate reactive oxygen species within recipient T cells. These findings support a potential novel mechanism of cell-cell communication involving exosomal transfer of mitochondria and the bioenergetic and/or redox regulation of target cells.

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Extracellular vesicles and asthma: A review of the literature

“…Free radical–generating MDRCs are known to regulate activities of T cells and airway responses in asthma (Table ) . While most previous research has focussed on mechanisms of communication through oxidant pathways and soluble mediators, a study by Hough et al have found that exosome‐mediated intercellular transfer could also be a mechanism by which MDRCs in asthmatics can communicate with T cells and signal T cell proliferation. Since mitochondria are capable of secreting ROS and play a role in the inflammatory response, the study aimed to measure mitochondrial transfer in exosomes derived from MDRCs of asthmatics.…”

New insight into the role of extracellular vesicles in kidney disease

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