调节性B细胞控制鼠哮喘模型中气道高反应性和肺部重塑
2020/12/17
摘要
背景： 哮喘是一种广泛的、多因素的慢性气道疾病。调节性B细胞(Bregs)对哮喘气道高反应性(AHR)和重塑的影响知之甚少。
目的：我们分析了B细胞在尘螨（HDM）诱导的小鼠哮喘模型中的作用。
方法：采用野生型（WT）和B细胞缺陷型（μMT）小鼠，将IL-10高表达型和IL-10缺陷型B细胞移植到B细胞缺陷型小鼠体内，分析B细胞对肺功能、组织重塑和免疫应答的影响。
结果：经HDM致敏后，野生型和B细胞缺陷型小鼠均出现了AHR，但B细胞缺陷型小鼠中的AHR明显更强，这一点已被两项独立的技术所证实:体内有创性肺功能检测和离体精确切割肺切片。此外，过敏性B细胞缺陷型小鼠的气道重塑显著增加，表现为气道胶原沉积增加，而调节FoxP3+和FoxP3- IL-10分泌的T细胞（Tregs）减少。在HDM致敏前，将IL-10高表达型而非IL-10缺陷型B细胞过继转移到B细胞缺陷型小鼠体内，减弱了AHR和肺部重塑。相反，FoxP3+ Tregs被IL-10高表达型和IL-10缺陷型B细胞的转移同等上调。
结论：我们在小鼠哮喘模型中的数据说明了Bregs在控制肺功能和气道重塑中的核心作用，并且可能支持B细胞靶向预防和治疗过敏性哮喘策略的未来概念。
Regulatory B cells control airway hyperreactivity and lung remodeling in a murine asthma model
Anika Habener Dipl-Biol, Christine Happle, Ruth Margarethe Grychtol, Jelena Skuljec, Mandy Busse, Kathleen Dalüge, Helena Obernolte, Katherina Sewald, Armin Braun, Almut Meyer-Bahlburg, Gesine Hansen.
Abstract
BACKGROUND:Asthma is a widespread, multifactorial chronic airway disease. The influence of regulatory B cells (Bregs) on airway hyperreactivity (AHR) and remodeling in asthma is poorly understood.
OBJECTIVE:We analyzed the role of B cells in a house dust mite (HDM)-based murine asthma model.
METHODS:By employing wildtype (WT) and B cell-deficient (μMT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to μMT mice, the influence of B cells on lung function, tissue remodeling and the immune response was analyzed.
RESULTS:After HDM-sensitization, both WT and μMT mice developed AHR, but AHR was significantly stronger in μMT mice as confirmed by two independent techniques: invasive lung function measurement in vivo and precision-cut lung slices ex vivo. Moreover, airway remodeling was significantly increased in allergic μMT mice as shown by enhanced collagen deposition in the airways, while regulatory FoxP3+ and FoxP3- IL-10-secreting T cells (Tregs) were reduced. Adoptive transfer of IL-10-proficient, but not IL-10-deficient B cells into μMT mice prior to HDM-sensitization, attenuated AHR and lung remodeling. In contrast, FoxP3+ Tregs were equally upregulated by transfer of IL-10-proficient as well as IL-10-deficient B cells.
CONCLUSION:Our data in a murine asthma model illustrate a central role of Bregs in the control of lung function and airway remodeling, and may support future concepts for B cell targeted prevention and treatment strategies for allergic asthma.
背景： 哮喘是一种广泛的、多因素的慢性气道疾病。调节性B细胞(Bregs)对哮喘气道高反应性(AHR)和重塑的影响知之甚少。
目的：我们分析了B细胞在尘螨（HDM）诱导的小鼠哮喘模型中的作用。
方法：采用野生型（WT）和B细胞缺陷型（μMT）小鼠，将IL-10高表达型和IL-10缺陷型B细胞移植到B细胞缺陷型小鼠体内，分析B细胞对肺功能、组织重塑和免疫应答的影响。
结果：经HDM致敏后，野生型和B细胞缺陷型小鼠均出现了AHR，但B细胞缺陷型小鼠中的AHR明显更强，这一点已被两项独立的技术所证实:体内有创性肺功能检测和离体精确切割肺切片。此外，过敏性B细胞缺陷型小鼠的气道重塑显著增加，表现为气道胶原沉积增加，而调节FoxP3+和FoxP3- IL-10分泌的T细胞（Tregs）减少。在HDM致敏前，将IL-10高表达型而非IL-10缺陷型B细胞过继转移到B细胞缺陷型小鼠体内，减弱了AHR和肺部重塑。相反，FoxP3+ Tregs被IL-10高表达型和IL-10缺陷型B细胞的转移同等上调。
结论：我们在小鼠哮喘模型中的数据说明了Bregs在控制肺功能和气道重塑中的核心作用，并且可能支持B细胞靶向预防和治疗过敏性哮喘策略的未来概念。
(中日友好医院呼吸与危重症医学科 王静茹 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2020 Nov 27; S0091-6749(20)31634-1. doi: 10.1016/j.jaci.2020.09.041.)
(J Allergy Clin Immunol. 2020 Nov 27; S0091-6749(20)31634-1. doi: 10.1016/j.jaci.2020.09.041.)
Regulatory B cells control airway hyperreactivity and lung remodeling in a murine asthma model
Anika Habener Dipl-Biol, Christine Happle, Ruth Margarethe Grychtol, Jelena Skuljec, Mandy Busse, Kathleen Dalüge, Helena Obernolte, Katherina Sewald, Armin Braun, Almut Meyer-Bahlburg, Gesine Hansen.
Abstract
BACKGROUND:Asthma is a widespread, multifactorial chronic airway disease. The influence of regulatory B cells (Bregs) on airway hyperreactivity (AHR) and remodeling in asthma is poorly understood.
OBJECTIVE:We analyzed the role of B cells in a house dust mite (HDM)-based murine asthma model.
METHODS:By employing wildtype (WT) and B cell-deficient (μMT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to μMT mice, the influence of B cells on lung function, tissue remodeling and the immune response was analyzed.
RESULTS:After HDM-sensitization, both WT and μMT mice developed AHR, but AHR was significantly stronger in μMT mice as confirmed by two independent techniques: invasive lung function measurement in vivo and precision-cut lung slices ex vivo. Moreover, airway remodeling was significantly increased in allergic μMT mice as shown by enhanced collagen deposition in the airways, while regulatory FoxP3+ and FoxP3- IL-10-secreting T cells (Tregs) were reduced. Adoptive transfer of IL-10-proficient, but not IL-10-deficient B cells into μMT mice prior to HDM-sensitization, attenuated AHR and lung remodeling. In contrast, FoxP3+ Tregs were equally upregulated by transfer of IL-10-proficient as well as IL-10-deficient B cells.
CONCLUSION:Our data in a murine asthma model illustrate a central role of Bregs in the control of lung function and airway remodeling, and may support future concepts for B cell targeted prevention and treatment strategies for allergic asthma.
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在哮喘模型中，直径≤2.5um的颗粒物通过靶向谷氨酸草酰乙酸转氨酶1和缺氧诱导因子1α来扰乱TH17/调节性T细胞的平衡
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环状RNA circHIPK3通过miR-326/STIMI轴调节气道平滑肌细胞的增值
