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Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells
- Source :
- Redox Biology, Vol 18, Iss, Pp 54-64 (2018), Redox Biology
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
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.<br />Graphical abstract fx1<br />Highlights • BAL and MDRC-derived exosomes contain mitochondria. • Airway exosomes contain mtDNA. • MDRC-derived exosomes transfer mitochondria to CD4+ T cells. • Exosomal mitochondria co-localize with host cell mitochondria.
- Subjects :
- 0301 basic medicine
BAL, Bronchoalveolar lavage
Mitochondrial DNA
Myeloid
T cell
Clinical Biochemistry
Inflammation
MitoT-Red, MitoTracker Red
Mitochondrion
Exosomes
Biochemistry
DCs, Dendritic cells
Derived Regulatory Cells
Green fluorescent protein
03 medical and health sciences
Mito-GFP, CellLight Mitochondria GFP
Immune system
medicine
lcsh:QH301-705.5
Myeloid-derived
EVs, Extracellular vesicles
MHC-II, Major histocompatibility complex-II
lcsh:R5-920
Chemistry
NTA, Nanoparticle tracking analysis
Organic Chemistry
MDRCs, Myeloid-derived regulatory cells
MSCs, Mesenchymal stem cells
MitoT-Green, MitoTracker Green
Asthma
Microvesicles
Mitochondria
3. Good health
Cell biology
030104 developmental biology
medicine.anatomical_structure
HLA-DR, Human Leukocyte Antigen – antigen D Related, MHC class II cell surface receptor encoded by the human leukocyte antigen complex
lcsh:Biology (General)
medicine.symptom
lcsh:Medicine (General)
Research Paper
ROS, Reactive oxygen species
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....b9d2c789b1f13e28ba94b02e41dd3dfe