Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice

• Published in: International immunopharmacology Vol. 91; p. 107288
• Main Authors: Ren, Jiling, Liu, Yongzhe, Yao, Ye, Feng, Lifeng, Zhao, Xiaotong, Li, Zongjin, Yang, Liang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2021; Elsevier BV
• Subjects: Alveoli; Animal models; Animals; Asthma; Asthma - chemically induced; Asthma - immunology; Asthma - metabolism; Asthma - prevention & control; Bisphosphonates; CCR2 protein; Cell Proliferation; Cells, Cultured; Clodronic acid; CX3C Chemokine Receptor 1 - genetics; CX3C Chemokine Receptor 1 - metabolism; CX3CR1 protein; Disease Models, Animal; Exosome; Exosomes; Exosomes - immunology; Exosomes - metabolism; Exosomes - transplantation; Flow cytometry; IL-10; Immunomodulation; Inflammation; Interleukin 10; Interleukin-10 - genetics; Interleukin-10 - metabolism; Lung - immunology; Lung - metabolism; Lung interstitial macrophages; Lungs; Macrophages; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; Mesenchymal Stem Cell Transplantation; Mesenchyme; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Monocyte chemoattractant protein 1; MSC; Ovalbumin; Respiratory tract diseases; Spleen; Spleen - immunology; Spleen - metabolism; Splenectomy; Stem cell transplantation; Stem cells; MSC; Exosome; Lung interstitial macrophages; IL-10; Asthma
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2020.107288

•MSC derived exosomes could inhibit allergic asthma in mice.•Lung interstitial macrophages ratios were enhanced by MSC derived exosomes.•Lung interstitial macrophages ratios were decreased in splenectomized mice.•The protection by MSC derived exosomes disappeared in Cx3cr1-IL-10-/-mice. Mesenchymal stem cells (MSCs) have been investigated in preventing and treating allergic asthma in many reports. Recently, MSC-derived exosomes (MSC-Exo) were showed a promising alternative to stem cell-based therapy in many kinds of diseases. However, the effect of MSC-Exo on allergic asthma has not been investigated thoroughly thus far. Here, we aimed to investigate the immunomodulation effect of MSC-Exo in a murine model of asthma and explore the underlying mechanisms. BALB/c mice were sensitized and challenged by OVA to establish asthma model. MSC-Exo were intranasally delivered before or during challenge and the protective effect were assessed after the last OVA challenge. Allergic airway inflammation elicited by OVA were significantly attenuated by intranasal delivery of MSC-Exo. To explore the protective mechanism of MSC-Exo, lung interstitial macrophages (IMs) and alveolar macrophages (AMs) were analyzed by flow cytometry and the origin of IMs were traced. Lung IMs ratios were significantly enhanced and high level of IL-10 was produced after MSC-Exo intranasal delivery. IMs ratios were not obviously affected by CCR2 inhibitor or Clodronate liposome administration, whereas significantly decreased in splenectomized mice. Cx3cr1+ cell specific IL-10 conditionally deficient mice were used to further examine the role of IL-10 producing IMs in allergic asthma. IMs-mediated protection was dependent on IL-10, given that the protection disappeared in Cx3cr1-IL-10-/-mice. In conclusion, intranasal delivery of MSC-Exo could substantially expand lung IL-10-producing IMs, which may originate from spleen, thus contribute to protection against allergic asthma in mice.