Exosomal transfer of mitochondria from airway myeloid-derived regulatory cells to T cells
Kenneth P. Hough,
Jennifer L. Trevor,
John G. Strenkowski,
Yong Wang,
Balu K. Chacko,
Sultan Tousif,
Diptiman Chanda,
Chad Steele,
Veena B. Antony,
Terje Dokland,
Xiaosen Ouyang,
Jianhua Zhang,
Steven R. Duncan,
Victor J. Thannickal,
Victor M. Darley-Usmar,
Jessy S. Deshane
Affiliations
Kenneth P. Hough
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jennifer L. Trevor
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
John G. Strenkowski
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Yong Wang
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Balu K. Chacko
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Sultan Tousif
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Diptiman Chanda
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Chad Steele
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Veena B. Antony
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Terje Dokland
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Xiaosen Ouyang
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jianhua Zhang
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Steven R. Duncan
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Victor J. Thannickal
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Victor M. Darley-Usmar
Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Jessy S. Deshane
Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Correspondence to: Department of Medicine, Division of Pulmonary Allergy and Critical Care Medicine, THT 433A, 1900 University Boulevard, University of Alabama at Birmingham, AL 35294, USA.
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. Keywords: Exosomes, Mitochondria, Asthma, Myeloid-derived, Derived Regulatory Cells
