Mice deficient in NOX2 display severe thymic atrophy, lymphopenia, and reduced lymphopoiesis in a zymosan-induced model of systemic inflammation.
Mice deficient in NOX2 display severe thymic atrophy, lymphopenia, and reduced lymphopoiesis in a zymosan-induced model of systemic inflammation.
复制标题
缺乏 NOX2 的小鼠在酵母聚糖诱导的全身炎症模型中表现出严重的胸腺萎缩、淋巴细胞减少和淋巴细胞生成减少。
DOI：
10.1007/s10753-020-01342-6
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发表时间：
2021
期刊：
影响因子：
5.1
通讯作者：
Y.
中科院分区：
文献类型：
--
作者：
Sugimoto;Y.;Endo;D.;and Aratani;Y.
吞噬细胞 NADPH 氧化酶突变的慢性肉芽肿病 (CGD) 患者由于活性氧产生减少而容易受到感染，并且在没有明显感染的情况下表现出自身免疫和炎症性疾病。中性粒细胞和巨噬细胞已被广泛研究，因为吞噬细胞 NADPH 氧化酶主要仅存在于其中，而其缺陷对淋巴细胞细胞结构的影响尚不清楚。我们在此展示了一种酵母聚糖诱导的全身炎症模型，与野生型小鼠相比，吞噬细胞NADPH氧化酶gp91phox亚基（NOX2）缺陷的CGD小鼠表现出更严重的胸腺萎缩，与外周血和脾淋巴细胞减少相关，并且骨髓中淋巴细胞生成减少。相反，与暴露于酵母聚糖的野生型小鼠相比，暴露于酵母聚糖的CGD小鼠出现更明显的中性粒细胞性肺部炎症、循环和脾脏中性粒细胞增多以及粒细胞生成增强。总体而言，这项研究提供的证据表明，在酵母聚糖诱导的全身炎症模型中，NOX2 缺乏会表现出严重的胸腺萎缩和淋巴细胞减少，并伴有中性粒细胞炎症增强。
Patients with chronic granulomatous disease (CGD) who have mutated phagocyte NADPH oxidase are susceptible to infections due to reduced reactive oxygen species production and exhibit autoimmune and inflammatory diseases in the absence of evident infection. Neutrophils and macrophages have been extensively studied since phagocyte NADPH oxidase is mainly found only in them, while the impact of its deficiency on lymphocyte cellularity is less well characterized. We showed herein a zymosan-induced systemic inflammation model that CGD mice deficient in the phagocyte NADPH oxidase gp91phox subunit (NOX2) exhibited more severe thymic atrophy associated with peripheral blood and splenic lymphopenia and reduced lymphopoiesis in the bone marrow in comparison with the wild-type mice. Conversely, the zymosan-exposed CGD mice suffered from more remarkable neutrophilic lung inflammation, circulating and splenic neutrophilia, and enhanced granulopoiesis compared with those in zymosan-exposed wild-type mice. Overall, this study provided evidence that NOX2 deficiency exhibits severe thymic atrophy and lymphopenia concomitant with enhanced neutrophilic inflammation in a zymosan-induced systemic inflammation model.