肺泡巨噬细胞清除凋亡细胞可防止屋尘螨诱导的哮喘性肺炎症的发生
2021/04/07
摘要
背景：凋亡细胞清除不良被认为是导致重症哮喘的原因之一，但肺吞噬细胞对凋亡细胞的摄取是否可以抑制屋尘螨(HDM)诱导的肺部炎症尚未被证实。
目的：本项目研究了小鼠肺内凋亡细胞的吞噬是否影响变应原诱导的哮喘气道炎症的发展，以及哪些免疫调节机制被激活。
方法：凋亡细胞被注入到HDM变应原激发的小鼠肺中，检测肺部炎症及抑制性分子表达，监测调节性T细胞的诱导。此外，一种腺苷受体激动剂被用来研究凋亡细胞的抑制作用机制。
结果：肺泡巨噬细胞对凋亡细胞的摄取抑制了HDM驱动的过敏性哮喘。这与促进调节性T细胞诱导分子视磺酸，抑制炎症细胞因子的产生，并使巨噬细胞更容易接受腺苷的抑制信号有关。相应地，腺苷受体激动剂治疗也通过作用于肺泡巨噬细胞限制了HDM驱动的过敏性气道炎症。
结论：这些数据为肺巨噬细胞抑制过敏原诱导的气道炎症机制提供了线索。它们提示以肺巨噬细胞为靶点，增加其吞噬能力，增强其生成视磺酸的能力，抑制其生成炎性细胞因子的能力，并增加其对腺苷的反应，可能有助于抑制过敏反应。
关键词：凋亡细胞清除；腺苷；肺泡巨噬细胞；哮喘；调节性T细胞。
Clearance of apoptotic cells by lung alveolar macrophages prevents development of house dust mite-induced asthmatic lung inflammation
Haruka Miki, Hong Pei, Donald Tom Gracias, Joel Linden, Michael Croft.
J Allergy Clin Immunol. 2021 Mar;147(3):1087-1092.e3. doi:10.1016/j.jaci.2020.10.005. Epub 2020 Oct 13.
Abstract
Background: Poor clearance of apoptotic cells has been suggested to contribute to severe asthma, but whether uptake of apoptotic cells by lung phagocytes might dampen house dust mite (HDM)-induced lung inflammation has not been shown.
Objectives: This study investigated whether apoptotic cell engulfment in the murine lung impacts the development of allergen-induced asthmatic airway inflammation and which immune modulating mechanisms were activated.
Methods: Apoptotic cells were infused into the lungs of mice challenged with HDM allergen and lung inflammation, expression of suppressive molecules, and induction of regulatory T cells were monitored. Additionally, an adenosine receptor agonist was tested to study the mechanism of suppression elicited by apoptotic cells.
Results: Apoptotic cell uptake by lung alveolar macrophages suppressed HDM-driven allergic asthma. This was associated with promoting the regulatory T cell-inducing molecule retinoic acid, inhibiting inflammatory cytokine production, and making macrophages more susceptible to receiving suppressive signals from adenosine. Correspondingly, adenosine receptor agonist treatment also limited HDM-driven allergic airway inflammation through an action on alveolar macrophages.
Conclusions: These data provide insight into the mechanisms by which lung macrophages dampen allergen-induced airway inflammation. They suggest that targeting lung macrophages to increase their phagocytic capacity, enhance their ability to make retinoic acid, dampen their capacity to make inflammatory cytokines, and increase their responsiveness to adenosine, could be useful to suppress allergic responses.
Keywords: Apoptotic cell clearance; adenosine; alveolar macrophage; asthma; regulatory T cell.
背景：凋亡细胞清除不良被认为是导致重症哮喘的原因之一，但肺吞噬细胞对凋亡细胞的摄取是否可以抑制屋尘螨(HDM)诱导的肺部炎症尚未被证实。
目的：本项目研究了小鼠肺内凋亡细胞的吞噬是否影响变应原诱导的哮喘气道炎症的发展，以及哪些免疫调节机制被激活。
方法：凋亡细胞被注入到HDM变应原激发的小鼠肺中，检测肺部炎症及抑制性分子表达，监测调节性T细胞的诱导。此外，一种腺苷受体激动剂被用来研究凋亡细胞的抑制作用机制。
结果：肺泡巨噬细胞对凋亡细胞的摄取抑制了HDM驱动的过敏性哮喘。这与促进调节性T细胞诱导分子视磺酸，抑制炎症细胞因子的产生，并使巨噬细胞更容易接受腺苷的抑制信号有关。相应地，腺苷受体激动剂治疗也通过作用于肺泡巨噬细胞限制了HDM驱动的过敏性气道炎症。
结论：这些数据为肺巨噬细胞抑制过敏原诱导的气道炎症机制提供了线索。它们提示以肺巨噬细胞为靶点，增加其吞噬能力，增强其生成视磺酸的能力，抑制其生成炎性细胞因子的能力，并增加其对腺苷的反应，可能有助于抑制过敏反应。
关键词：凋亡细胞清除；腺苷；肺泡巨噬细胞；哮喘；调节性T细胞。
(刘影1 张红萍1 王刚2 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（J Allergy Clin Immunol. 2021 Mar;147(3):1087-1092.e3. doi:10.1016/j.jaci.2020.10.005. Epub 2020 Oct 13.）
（J Allergy Clin Immunol. 2021 Mar;147(3):1087-1092.e3. doi:10.1016/j.jaci.2020.10.005. Epub 2020 Oct 13.）
Clearance of apoptotic cells by lung alveolar macrophages prevents development of house dust mite-induced asthmatic lung inflammation
Haruka Miki, Hong Pei, Donald Tom Gracias, Joel Linden, Michael Croft.
J Allergy Clin Immunol. 2021 Mar;147(3):1087-1092.e3. doi:10.1016/j.jaci.2020.10.005. Epub 2020 Oct 13.
Abstract
Background: Poor clearance of apoptotic cells has been suggested to contribute to severe asthma, but whether uptake of apoptotic cells by lung phagocytes might dampen house dust mite (HDM)-induced lung inflammation has not been shown.
Objectives: This study investigated whether apoptotic cell engulfment in the murine lung impacts the development of allergen-induced asthmatic airway inflammation and which immune modulating mechanisms were activated.
Methods: Apoptotic cells were infused into the lungs of mice challenged with HDM allergen and lung inflammation, expression of suppressive molecules, and induction of regulatory T cells were monitored. Additionally, an adenosine receptor agonist was tested to study the mechanism of suppression elicited by apoptotic cells.
Results: Apoptotic cell uptake by lung alveolar macrophages suppressed HDM-driven allergic asthma. This was associated with promoting the regulatory T cell-inducing molecule retinoic acid, inhibiting inflammatory cytokine production, and making macrophages more susceptible to receiving suppressive signals from adenosine. Correspondingly, adenosine receptor agonist treatment also limited HDM-driven allergic airway inflammation through an action on alveolar macrophages.
Conclusions: These data provide insight into the mechanisms by which lung macrophages dampen allergen-induced airway inflammation. They suggest that targeting lung macrophages to increase their phagocytic capacity, enhance their ability to make retinoic acid, dampen their capacity to make inflammatory cytokines, and increase their responsiveness to adenosine, could be useful to suppress allergic responses.
Keywords: Apoptotic cell clearance; adenosine; alveolar macrophage; asthma; regulatory T cell.
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