Center of Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif.
Center of Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, Calif; Department of Medicine, University of California San Diego, La Jolla, Calif.
J Allergy Clin Immunol. 2021 Mar;147(3):1087-1092.e3. doi: 10.1016/j.jaci.2020.10.005. Epub 2020 Oct 13.
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.
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.
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.
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.
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.
凋亡细胞清除不良被认为与严重哮喘有关，但肺吞噬细胞摄取凋亡细胞是否会抑制屋尘螨（HDM）诱导的肺部炎症尚未得到证实。
本研究旨在探讨肺部吞噬凋亡细胞是否会影响变应原诱导的哮喘气道炎症的发生，并研究激活的免疫调节机制。
将凋亡细胞注入到接受 HDM 变应原挑战的小鼠肺部，监测肺部炎症、抑制性分子的表达以及调节性 T 细胞的诱导。此外，还测试了一种腺苷受体激动剂，以研究凋亡细胞诱导的抑制机制。
肺肺泡巨噬细胞摄取凋亡细胞可抑制 HDM 驱动的变应性哮喘。这与促进调节性 T 细胞诱导分子维甲酸的产生、抑制炎症细胞因子的产生以及使巨噬细胞更容易接受来自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来限制 HDM 驱动的变应性气道炎症。
这些数据提供了对肺巨噬细胞抑制变应原诱导的气道炎症的机制的深入了解。它们表明，靶向肺巨噬细胞以增加其吞噬能力、增强其产生维甲酸的能力、抑制其产生炎症细胞因子的能力以及增加其对腺苷的反应性，可能有助于抑制过敏反应。
