生命早期活化的嗜酸性粒细胞会损害肺部发育并促进长期肺损伤。

IF 7.9 2区 医学 Q1 IMMUNOLOGY
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引用次数: 0

摘要

2型免疫反应的加剧会促进肺部炎症和肺部发育的改变;然而,尽管嗜酸性粒细胞在出生后肺部扩大,但尚未对新生儿肺部疾病进行专门评估。此外,包括早产和呼吸道感染在内的生命早期因素使婴儿日后易患慢性阻塞性肺病。为了评估发育中肺部的嗜酸性粒细胞及其对慢性肺病的影响,我们培育了嗜酸性粒细胞特异性缺失负调控酶 SHIP-1 的小鼠。这增加了发育中肺部嗜酸性粒细胞的活性和数量,导致肺发育受损、活化肺泡巨噬细胞(AMφ)扩张、多核巨细胞形成、气孔扩大和纤维化。尽管嗜酸性粒细胞在肺发育完成后有所减少,但以 AMφ 为主的炎症仍持续存在,同时还伴有肺损伤。骨髓嵌合体研究表明,SHIP-1缺陷的嗜酸性粒细胞不足以驱动成年稳态小鼠的肺部炎症,但炎症和损伤一旦出现,就无法解决。在肺泡化过程中消耗嗜酸性粒细胞可缓解肺部炎症和肺部病理变化,这证明了嗜酸性粒细胞的内在效应。这些结果表明,肺泡化过程中活化的嗜酸性粒细胞会加重 AMφs,并促进持续的炎症和长期的肺部病变。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Activated eosinophils in early life impair lung development and promote long-term lung damage
Exaggeration of type 2 immune responses promotes lung inflammation and altered lung development; however, eosinophils, despite expansion in the postnatal lung, have not been specifically assessed in the context of neonatal lung disease. Furthermore, early life factors including prematurity and respiratory infection predispose infants to chronic obstructive pulmonary disease later in life. To assess eosinophils in the developing lung and how they may contribute to chronic lung disease, we generated mice harboring eosinophil-specific deletion of the negative regulatory enzyme SH2 domain-containing inositol 5′ phosphatase-1. This increased the activity and number of pulmonary eosinophils in the developing lung, which was associated with impaired lung development, expansion of activated alveolar macrophages (AMφ), multinucleated giant cell formation, enlargement of airspaces, and fibrosis. Despite regression of eosinophils following completion of lung development, AMφ-dominated inflammation persisted, alongside lung damage. Bone marrow chimera studies showed that SH2 domain-containing inositol 5′ phosphatase-1-deficient eosinophils were not sufficient to drive inflammatory lung disease in adult steady-state mice but once inflammation and damage were present, it could not be resolved. Depletion of eosinophils during alveolarization alleviated pulmonary inflammation and lung pathology, demonstrating an eosinophil-intrinsic effect. These results show that the presence of activated eosinophils during alveolarization aggravates AMφs and promotes sustained inflammation and long-lasting lung pathology.
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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