CD8α+CD11c+ Extracellular Vesicles in the Lungs Control Immune Homeostasis of the Respiratory Tract via TGF-β1 and IL-10.

The immune balance of the respiratory tract is strictly regulated. Extracellular vesicles (EVs) have been reported to participate in maintaining the immune balance in the intestinal tract, but whether they are involved in regulation of the immune balance in the respiratory tract has yet to be revealed. In this study, we found that physiological EVs from lungs of WT mice (L-EVs) could be isolated, which contained the immunosuppressive cytokines TGF-β1 and IL-10. Among L-EV subsets, only the CD8α+CD11c+ EV subset was positive for TGF-β1 and IL-10 and could inhibit CD4+ T cell proliferation via TGF-β1 in vitro and relieve murine asthmatic symptoms. Mechanistically, L-EVs were effective at inhibiting OVA peptide-specific CD4+ T cell proliferation in a TGF-β1- and IL-10-dependent manner. In addition, they could prevent CD4+ T cells from hilar lymph nodes from secreting IL-4, IL-9, and IL-17A via IL-10 ex vivo, suggesting inhibition of Th2, Th9, and Th17 cell responses. Altogether, our results indicate that EVs from the lungs are involved in control of the immune balance in the respiratory tract, which reveals a novel mechanism in the maintenance of respiratory tract immune homeostasis.