Ablation of IL-33 Suppresses Th2 Responses but Is Accompanied by Sustained Mucus Obstruction in the Scnn1b Transgenic Mouse Model.
Ablation of IL-33 Suppresses Th2 Responses but Is Accompanied by Sustained Mucus Obstruction in the Scnn1b Transgenic Mouse Model.
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DOI：
10.4049/jimmunol.1900234
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发表时间：
2020-03-15
期刊：
影响因子：
--
通讯作者：
Saini Y
中科院分区：
文献类型：
--
作者：
Lewis BW;Vo T;Choudhary I;Kidder A;Bathula C;Ehre C;Wakamatsu N;Patial S;Saini Y
囊性纤维化（CF）的特征是气道表面液体（ASL）层脱水并伴有持续的粘液阻塞。t -辅助性2 （Th2）免疫反应通常表现为黏液细胞密度增加[黏液细胞化生（mucous cell metaplasia， MCM）]并伴有黏液阻塞。白细胞介素33 （IL33）是一种已知的Th2免疫反应诱导剂，但其在cf样肺部疾病模型（即scn1b -Tg+ (Tg+)小鼠）中粘液阻塞和相关表型中的作用尚不清楚。因此，对il33敲除（IL33KO） Tg+小鼠进行检测，并与il33杂合（IL33HET） Tg+小鼠进行比较。与IL33HET/Tg+小鼠相比，IL33KO/Tg+小鼠的BALF嗜酸性粒细胞完全缺失，IL5（与嗜酸性粒细胞分化和募集相关的细胞因子）和IL4（主要的Th2细胞因子）的BALF浓度显著降低。与IL33HET/Tg+小鼠相比，IL33KO/Tg+小鼠th2相关基因信号（Slc26a4、Clca1、Retnla和chi314）水平显著降低，气道上皮细胞内粘膜多糖染色完全丧失。与IL33HET/Tg+小鼠相比，IL33KO/Tg+小鼠MUC5AC蛋白表达水平显著降低，但粘液阻塞程度、MUC5B蛋白表达、细菌负担和新生儿死亡率均未降低。有趣的是，与IL33HET/Tg+小鼠相比，IL33KO/Tg+小鼠的组织学特征，包括亚上皮性气道炎症和肺泡间隙增大，在一定程度上被夸大了。综上所述，我们的数据表明，虽然IL33调节Th2炎症反应和MUC5AC蛋白的产生，但粘液阻塞并不依赖于IL33。
Cystic fibrosis (CF) is characterized by dehydration of the airway surface liquid (ASL) layer with persistent mucus obstruction. T-helper 2 (Th2) immune responses are often manifested as increased mucous cell density [mucous cell metaplasia (MCM)] associated with mucus obstruction. Interleukin 33 (IL33) is a known inducer of Th2 immune responses but its roles in mucus obstruction and related phenotypes in a CF-like lung disease model, i.e., Scnn1b-Tg+ (Tg+) mouse, remains unclear. Accordingly, IL33-knockout (IL33KO) Tg+ mice were examined and compared with IL33-heterozygous (IL33HET) Tg+ mice. As compared to IL33HET/Tg+ mice, the IL33KO/Tg+ mice had complete absence of BALF eosinophilia, accompanied with significant reduction in BALF concentration of IL5, a cytokine associated with eosinophil differentiation and recruitment, and IL4, a major Th2 cytokine. As compared to IL33HET/Tg+ mice, IL33KO/Tg+ mice had significantly reduced levels of Th2-associated gene signatures (Slc26a4, Clca1, Retnla, and Chi3l4), along with complete loss of intracellular muco-polysaccharide staining in the airway epithelium. As compared to IL33HET/Tg+ mice, while the IL33KO/Tg+ mice had significantly reduced levels of MUC5AC protein expression, they showed no reduction in the degree of mucus obstruction, MUC5B protein expression, bacterial burden, and neonatal mortality. Interestingly, the histological features including sub-epithelial airway inflammation and alveolar space enlargement were somewhat exaggerated in IL33KO/Tg+ mice compared to IL33HET/Tg+ mice. Taken together, our data indicate that while IL33 modulates Th2 inflammatory responses and MUC5AC protein production, mucus obstruction is not dependent on IL33.
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影响因子：
8
作者：
通讯作者：
--
粘液浓度和分泌的粘蛋白MUC5AC和MUC5B对粘液刺激性肺部疾病的发病机理的贡献。
影响因子：
8
作者：
Livraghi-Butrico A;Grubb BR;Wilkinson KJ;Volmer AS;Burns KA;Evans CM;O'Neal WK;Boucher RC
通讯作者：
Boucher RC
DOI：
10.1164/rccm.200708-1233oc
发表时间：
2008-04-01
影响因子：
24.7
作者：
Mall, Marcus A.;Harkema, Jack R.;Boucher, Richard C.
通讯作者：
Boucher, Richard C.
影响因子：
11.1
作者：
Boucher, R. C.
通讯作者：
Boucher, R. C.
影响因子：
3.6
作者：
Lan, Fang;Yuan, Baohong;Yin, Hui
通讯作者：
Yin, Hui