MSC产生的外泌体可通鼻内注射使小鼠产生分泌IL-10的肺间质巨噬细胞来减轻过敏性哮喘
2021/03/22
摘要
背景：在许多报道中，已经研究了间充质干细胞（MSC）在预防和治疗过敏性哮喘中的作用。最近，在许多疾病中，MSC衍生的外泌体（MSC-Exo）被证明是一种基于干细胞疗法的有前途的替代方法。但是，到目前为止，尚未对MSC-Exo对过敏性哮喘的作用进行彻底研究。
目的：在这里，我们旨在研究MSC-Exo在哮喘小鼠模型中的免疫调节作用，并探讨其潜在机制。
方法：将BALB/c小鼠致敏并通过OVA攻击以建立哮喘模型。 MSC-Exo在激发前或激发期间经鼻内注射，并在最后一次OVA激发后评估其保护作用。为了探索MSC-Exo的保护机制，通过流式细胞术分析了肺间质巨噬细胞（IMs）和肺泡巨噬细胞（AMs），并追踪了IMs的起源。
结果：MSCExo鼻内给药后，肺IMs比率显着提高，并产生高水平的IL-10。 IMs比率受CCR2抑制剂或氯膦酸盐脂质体给药的影响不明显，而在脾切除的小鼠中IMs的比率则显着降低。使用Cx3cr1 +细胞特异性IL-10条件缺陷小鼠进一步验证IL-10产生IM在过敏性哮喘中的作用。IMs介导的保护依赖于IL-10，因为该保护在Cx3cr1-IL-10-/-小鼠中消失了。
结论：综上所述，鼻腔内递送MSC-Exo可能会大大增多肺中能产生IL-10的IM，这些IM可能源自脾脏，有助于保护小鼠免受过敏性哮喘的侵害。
Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice
Ladjemi MZ, Di Candia L, Heddebaut N, et al.
Abstract
Background: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.
Objective:Here, we aimed to investigate the immunomodulation effect of MSC-Exo in a murine model of asthma and explore the underlying mechanisms.
Methods: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.
Results:Lung IMs ratios were significantly enhanced and high level of IL-10 was produced after MSCExo 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.
Conclusion: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.
背景：在许多报道中，已经研究了间充质干细胞（MSC）在预防和治疗过敏性哮喘中的作用。最近，在许多疾病中，MSC衍生的外泌体（MSC-Exo）被证明是一种基于干细胞疗法的有前途的替代方法。但是，到目前为止，尚未对MSC-Exo对过敏性哮喘的作用进行彻底研究。
目的：在这里，我们旨在研究MSC-Exo在哮喘小鼠模型中的免疫调节作用，并探讨其潜在机制。
方法：将BALB/c小鼠致敏并通过OVA攻击以建立哮喘模型。 MSC-Exo在激发前或激发期间经鼻内注射，并在最后一次OVA激发后评估其保护作用。为了探索MSC-Exo的保护机制，通过流式细胞术分析了肺间质巨噬细胞（IMs）和肺泡巨噬细胞（AMs），并追踪了IMs的起源。
结果：MSCExo鼻内给药后，肺IMs比率显着提高，并产生高水平的IL-10。 IMs比率受CCR2抑制剂或氯膦酸盐脂质体给药的影响不明显，而在脾切除的小鼠中IMs的比率则显着降低。使用Cx3cr1 +细胞特异性IL-10条件缺陷小鼠进一步验证IL-10产生IM在过敏性哮喘中的作用。IMs介导的保护依赖于IL-10，因为该保护在Cx3cr1-IL-10-/-小鼠中消失了。
结论：综上所述，鼻腔内递送MSC-Exo可能会大大增多肺中能产生IL-10的IM，这些IM可能源自脾脏，有助于保护小鼠免受过敏性哮喘的侵害。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（J Allergy Clin Immunol, 2021.）
（J Allergy Clin Immunol, 2021.）
Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice
Ladjemi MZ, Di Candia L, Heddebaut N, et al.
Abstract
Background: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.
Objective:Here, we aimed to investigate the immunomodulation effect of MSC-Exo in a murine model of asthma and explore the underlying mechanisms.
Methods: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.
Results:Lung IMs ratios were significantly enhanced and high level of IL-10 was produced after MSCExo 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.
Conclusion: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.
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TRPA1抑制剂通过抑制哮喘治疗中的神经源性炎症和气道收缩治疗哮喘
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缺氧的hUCMSC产生的细胞外囊泡减轻了慢性哮喘小鼠的过敏性气道炎症和气道重塑
