Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Hangzhou Medical College, Hangzhou 310053, Zhejiang, China.
J Immunol. 2018 Mar 1;200(5):1651-1660. doi: 10.4049/jimmunol.1701447. Epub 2018 Jan 22.
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 CD8αCD11c 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.
呼吸道的免疫平衡受到严格调控。已有研究报道，细胞外囊泡（EVs）参与维持肠道的免疫平衡，但它们是否参与调节呼吸道的免疫平衡尚未可知。在本研究中，我们发现可以从 WT 小鼠肺部分离出生理性 EVs（L-EVs），其中含有免疫抑制性细胞因子 TGF-β1 和 IL-10。在 L-EV 亚群中，只有 CD8αCD11c EV 亚群呈 TGF-β1 和 IL-10 阳性，并且能够通过 TGF-β1 体外抑制 CD4 T 细胞增殖，并缓解小鼠哮喘症状。从机制上讲，L-EVs 能够通过 TGF-β1 和 IL-10 依赖性方式有效抑制 OVA 肽特异性 CD4 T 细胞增殖。此外，它们还可以通过 IL-10 抑制来自肺门淋巴结的 CD4 T 细胞体外分泌 IL-4、IL-9 和 IL-17A，表明其抑制 Th2、Th9 和 Th17 细胞应答。综上所述，我们的研究结果表明，肺部来源的 EVs 参与了呼吸道免疫平衡的控制，揭示了维持呼吸道免疫稳态的新机制。
