On the path to predicting immune responses in the lung: Modeling the pulmonary innate immune system at the air-liquid interface (ALI).

On the path to predicting immune responses in the lung: Modeling the pulmonary innate immune system at the air-liquid interface (ALI).
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DOI:
10.1016/j.ejps.2023.106596
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发表时间:
2023-12-01
影响因子:
4.6
通讯作者:
Fromen, Catherine A.
Fromen, Catherine A.
中科院分区:
医学2区
文献类型:
--
作者:
Graf, Jodi;Trautmann-Rodriguez, Michael;Sabnis, Simone;Kloxin, April M.;Fromen, Catherine A.

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慢性呼吸道疾病和感染是全球最大的死亡原因之一,其中许多疾病仍然无法治愈,包括慢性阻塞性肺病、特发性肺纤维化和呼吸道合胞病毒等。肺部治疗通过直接递送至作用部位,为治疗肺部感染和疾病提供了尚未开发的潜力。然而,创新呼吸系统疾病新治疗模式的能力将依赖于对人类肺部微环境进行建模,并包括导致疾病的关键细胞相互作用。肺微环境的一项关键特征是气液界面(ALI)。使用细胞培养插入物、类器官、微流体和精密肺切片 (PCLS) 的 ALI 接口建模技术正在迅速发展;然而,这些模型缺乏一个主要组成部分——先天免疫细胞群。巨噬细胞、中性粒细胞和树突状细胞等代表关键的肺细胞群,在肺部感染或损伤期间充当第一反应者。先天免疫细胞对基质细胞做出反应并调节基质细胞,并弥合先天免疫系统和适应性免疫系统之间的差距,控制身体对外来病原体和碎片的反应。在本文中,我们回顾了 ALI 培养系统的现状,重点关注先天免疫细胞,并提出了基于当前模型以增加复杂性和相关免疫细胞群的方法。
Chronic respiratory diseases and infections are among the largest contributors to death globally, many of which still have no cure, including chronic obstructive pulmonary disorder, idiopathic pulmonary fibrosis, and respiratory syncytial virus among others. Pulmonary therapeutics afford untapped potential for treating lung infection and disease through direct delivery to the site of action. However, the ability to innovate new therapeutic paradigms for respiratory diseases will rely on modeling the human lung microenvironment and including key cellular interactions that drive disease. One key feature of the lung microenvironment is the air-liquid interface (ALI). ALI interface modeling techniques, using cell-culture inserts, organoids, microfluidics, and precision lung slices (PCLS), are rapidly developing; however, one major component of these models is lacking—innate immune cell populations. Macrophages, neutrophils, and dendritic cells, among others, represent key lung cell populations, acting as the first responders during lung infection or injury. Innate immune cells respond to and modulate stromal cells and bridge the gap between the innate and adaptive immune system, controlling the bodies response to foreign pathogens and debris. In this article, we review the current state of ALI culture systems with a focus on innate immune cells and suggest ways to build on current models to add complexity and relevant immune cell populations.
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