Source: openalex · Kenneth P. Hough, Jennifer Trevor, Shaheer Ahmad, Yong Wang, Balu K. Chacko · Nature Communications · 2026-05-26
URL: https://doi.org/10.1038/s41467-026-73684-y
AI rationale (5/5, tier: emerging): Directly demonstrates mitochondrial transfer between cells and ROS-dependent signaling as functional mechanism in human immune cells.
Abstract Small extracellular vesicles (sEVs) orchestrate cell-cell communication, but the role of sEV signaling via mitochondria in perpetuating asthmatic airway inflammation is unknown. Myeloid-derived regulatory cells (MDRCs) control CD4 + T cell responses in asthma. We demonstrate that airway MDRC-derived sEVs from asthmatics mediate T cell receptor engagement and transfer of mitochondria that induce antigen-specific activation and polarization of Th17 and Th2 cells. sEV-dependent T cell activation and Th polarization were mediated by mitochondrial oxidant-dependent NF-κB signaling, which, when blocked, mitigated CD4 + T cell activation. Mitochondrial fission regulator, DRP-1, promoted mitochondrial packaging within MDRC-sEVs. Internalized sEVs co-localized with the polarized cytoskeleton and mitochondrial networks in recipient T cells. Intranasal transfer of mitochondria packaged sEVs enhanced allergic airway inflammation and Th polarization in a murine asthma model. Our studies indicate a previously unrecognized role for mitochondrial fission and sEV- mitochondria-mediated signaling in dysregulated T cell activation, Th polarization, and pathology in asthma.