Exosomal Transfer of Mitochondria Reprograms T Helper Cell Function In Chronic Airway Inflammation

Myeloid-derived regulatory cells (MDRCs) are regulators of CD4+ T cell responses in asthma. Here, we demonstrate that airway MDRC-derived exosomes from asthmatics mediate T cell receptor engagement and mitochondrial transfer that promote antigen-specific activation and polarization of Th17 and Th2 cells, drivers of chronic airway inflammation in asthma.

Exosomal mitochondria are internalized by CD4+ T cells predominantly by membrane fusion, although their activation is internalization-independent. Additionally, blocking mitochondrial oxidant signaling in MDRC-derived exosomes mitigates T cell activation. In asthmatics, a Drp1-dependent mitochondrial fission process in pro-inflammatory MDRCs generates exosomal mitochondria.