The Innate Lymphoid System Is a Critical Player in the Manifestation of Mucoinflammatory Airway Disease in Mice.
The Innate Lymphoid System Is a Critical Player in the Manifestation of Mucoinflammatory Airway Disease in Mice.
复制标题
DOI：
10.4049/jimmunol.2000530
复制
发表时间：
2020-09-15
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;Choudhary I;Paudel K;Mao Y;Sharma R;Wang Y;Deshane JS;Boucher RC;Patial S;Saini Y
已知先天性淋巴和适应性免疫细胞调节上皮反应，包括粘液细胞化生（MCM），但它们在粘膜炎性气道疾病（例如囊性纤维化（CF））中的作用仍然未知。Scnn 1b-Tg+（Tg+）小鼠，重现CF样粘膜炎性气道疾病，先天淋巴（IL 2 rgKO），适应性免疫（Rag 1 KO），或两个系统（IL 2 rgKO/Rag 1 KO）缺陷，研究其各自的贡献，在粘膜炎性气道疾病的发病机制。如前所述，免疫活性Tg+青少年表现出自发性新生儿细菌感染，具有强烈的粘膜炎症特征，包括Th 2相关标志物表达升高，伴有MCM，MUC 5 B表达升高和气道粘液阻塞。Il 2 rgKO/Tg+青少年中的细菌负荷增加，但在Il 2 rgKO/Rag 1 KO/Tg+青少年中恢复到显著较低的水平。从机制上讲，这种改善反映了适应性免疫衍生的IL-10的产生减少，进而增加了巨噬细胞的活化。尽管免疫活性Tg+和Rag 1 KO/Tg+幼体之间的所有粘膜炎症特征相当，但Il 2 rgKO/Tg+和Il 2 rgKO/Rag 1 KO/Tg+幼体表现出Th 2标记物表达水平受抑制、MCM减少、MUC 5 B表达受抑制和粘液阻塞减少。总的来说，这些数据表明，在气道粘液阻塞的情况下，适应性免疫系统抑制抗菌巨噬细胞活化，而先天淋巴系统有助于MCM，粘蛋白产生和粘液阻塞。
Innate lymphoid and adaptive immune cells are known to regulate epithelial responses, including mucous cell metaplasia (MCM), but their roles in muco-inflammatory airway diseases, such as cystic fibrosis (CF), remain unknown. Scnn1b-Tg+ (Tg+) mice, that recapitulate CF-like muco-inflammatory airway disease, deficient in innate lymphoid (Il2rgKO), adaptive immune (Rag1KO), or both systems (Il2rgKO/Rag1KO), were employed to investigate their respective contributions in the pathogenesis of muco-inflammatory airway disease. As previously reported, immunocompetent Tg+ juveniles exhibited spontaneous neonatal bacterial infections with robust muco-inflammatory features, including elevated expression of Th2-associated markers accompanied by MCM, elevated MUC5B expression, and airway mucus obstruction. The bacterial burden was increased in Il2rgKO/Tg+ juveniles but returned to significantly lower levels in Il2rgKO/Rag1KO/Tg+ juveniles. Mechanistically, this improvement reflected reduced production of adaptive immunity-derived IL-10 and, in turn, increased activation of macrophages. While all the muco-inflammatory features were comparable between the immunocompetent Tg+ and Rag1KO/Tg+ juveniles, the Il2rgKO/Tg+ and Il2rgKO/Rag1KO/Tg+ juveniles exhibited suppressed expression levels of Th2 markers, diminished MCM, suppressed MUC5B expression, and reduced mucus obstruction. Collectively, these data indicate that, in the context of airway mucus obstruction, the adaptive immune system suppresses antibacterial macrophage activation, whereas the innate lymphoid system contributes to MCM, mucin production, and mucus obstruction.
登录
查看更多内容
DOI：
10.4049/jimmunol.1900234
发表时间：
2020-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lewis BW;Vo T;Choudhary I;Kidder A;Bathula C;Ehre C;Wakamatsu N;Patial S;Saini Y
通讯作者：
Saini Y
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
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.