白细胞介素-9促进过敏性气道炎症中肥大细胞祖细胞增殖和CCR2依赖性肥大细胞迁移
2023/05/25
摘要
过敏性哮喘是一种慢性肺部疾病，其特征是气道高反应性和细胞浸润，IgE依赖性肥大细胞激活加剧了这种情况。白细胞介素-9（IL-9）在过敏性炎症期间促进肥大细胞扩张，但IL-9如何扩张组织肥大细胞并促进肥大细胞功能尚不清楚。在本报告中，使用多种过敏性气道炎症模型，我们发现成熟肥大细胞（mMCs）和肥大细胞前体（MCp）都表达IL-9R，并在过敏性炎症期间对IL-9作出反应。IL-9作用于骨髓和肺中的MCp以增强增殖能力。此外，肺中的IL-9刺激CCR2+mMC从骨髓动员并募集到过敏性肺组织。混合骨髓嵌合体证明这些是MCp和mMC群体中的内在效应。在过敏性炎症的情况下，产生IL-9的T细胞对于增加肺中的肥大细胞数量是必要的，也是足够的。重要的是，T细胞IL-9介导的肥大细胞扩增是抗原诱导和肥大细胞依赖性气道高反应性发展所必需的。总之，这些数据表明，T细胞IL-9通过直接影响MCp的增殖和mMC的迁移来诱导肺肥大细胞的扩增和迁移，从而介导气道高反应性。
Interleukin-9 promotes mast cell progenitor proliferation and CCR2-dependent mast cell migration in allergic airway inflammation
Abigail Pajulas, Yongyao Fu, Cherry C L Cheung, Michelle Chu, Anthony Cannon, Nada Alakhras, Jilu Zhang, Benjamin J Ulrich, Andrew S Nelson, Baohua Zhou, Mark H Kaplan
Abstract
Allergic asthma is a chronic lung disease characterized by airway hyperresponsiveness and cellular infiltration that is exacerbated by IgE-dependent mast cell activation. Interleukin-9 (IL-9) promotes mast cell expansion during allergic inflammation but precisely how IL-9 expands tissue mast cells and promotes mast cell function is unclear. In this report, using multiple models of allergic airway inflammation, we show that both mature mast cells (mMCs) and mast cell precursors (MCp) express IL-9R and respond to IL-9 during allergic inflammation. IL-9 acts on MCp in the bone marrow and lungs to enhance proliferative capacity. Furthermore, IL-9 in the lung stimulates mobilization of CCR2+ mMC from the bone marrow and recruitment to the allergic lung. Mixed bone marrow chimeras demonstrate that these are intrinsic effects in the MCp and mMC populations. IL-9-producing T cells are both necessary and sufficient to increase mast cell numbers in the lung in the context of allergic inflammation. Importantly, T cell IL-9-mediated mast cell expansion is required for the development of antigen-induced and mast cell-dependent airway hyperreactivity. Collectively, these data demonstrate that T cell IL-9 induces lung mast cell expansion and migration by direct effects on the proliferation of MCp and the migration of mMC to mediate airway hyperreactivity.
过敏性哮喘是一种慢性肺部疾病，其特征是气道高反应性和细胞浸润，IgE依赖性肥大细胞激活加剧了这种情况。白细胞介素-9（IL-9）在过敏性炎症期间促进肥大细胞扩张，但IL-9如何扩张组织肥大细胞并促进肥大细胞功能尚不清楚。在本报告中，使用多种过敏性气道炎症模型，我们发现成熟肥大细胞（mMCs）和肥大细胞前体（MCp）都表达IL-9R，并在过敏性炎症期间对IL-9作出反应。IL-9作用于骨髓和肺中的MCp以增强增殖能力。此外，肺中的IL-9刺激CCR2+mMC从骨髓动员并募集到过敏性肺组织。混合骨髓嵌合体证明这些是MCp和mMC群体中的内在效应。在过敏性炎症的情况下，产生IL-9的T细胞对于增加肺中的肥大细胞数量是必要的，也是足够的。重要的是，T细胞IL-9介导的肥大细胞扩增是抗原诱导和肥大细胞依赖性气道高反应性发展所必需的。总之，这些数据表明，T细胞IL-9通过直接影响MCp的增殖和mMC的迁移来诱导肺肥大细胞的扩增和迁移，从而介导气道高反应性。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Mucosal Immunol. 2023 May 10;S1933-0219(23)00033-8. doi: 10.1016/j.mucimm.2023.05.002.)
(Mucosal Immunol. 2023 May 10;S1933-0219(23)00033-8. doi: 10.1016/j.mucimm.2023.05.002.)
Interleukin-9 promotes mast cell progenitor proliferation and CCR2-dependent mast cell migration in allergic airway inflammation
Abigail Pajulas, Yongyao Fu, Cherry C L Cheung, Michelle Chu, Anthony Cannon, Nada Alakhras, Jilu Zhang, Benjamin J Ulrich, Andrew S Nelson, Baohua Zhou, Mark H Kaplan
Abstract
Allergic asthma is a chronic lung disease characterized by airway hyperresponsiveness and cellular infiltration that is exacerbated by IgE-dependent mast cell activation. Interleukin-9 (IL-9) promotes mast cell expansion during allergic inflammation but precisely how IL-9 expands tissue mast cells and promotes mast cell function is unclear. In this report, using multiple models of allergic airway inflammation, we show that both mature mast cells (mMCs) and mast cell precursors (MCp) express IL-9R and respond to IL-9 during allergic inflammation. IL-9 acts on MCp in the bone marrow and lungs to enhance proliferative capacity. Furthermore, IL-9 in the lung stimulates mobilization of CCR2+ mMC from the bone marrow and recruitment to the allergic lung. Mixed bone marrow chimeras demonstrate that these are intrinsic effects in the MCp and mMC populations. IL-9-producing T cells are both necessary and sufficient to increase mast cell numbers in the lung in the context of allergic inflammation. Importantly, T cell IL-9-mediated mast cell expansion is required for the development of antigen-induced and mast cell-dependent airway hyperreactivity. Collectively, these data demonstrate that T cell IL-9 induces lung mast cell expansion and migration by direct effects on the proliferation of MCp and the migration of mMC to mediate airway hyperreactivity.
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严重哮喘ILC2s表现出经生物制剂修饰的增殖能力的增强
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气道高反应性反映哮喘表型中皮质类固醇敏感肥大细胞的参与
