IL-1β prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early-life rhinovirus infection in mice.
IL-1β prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early-life rhinovirus infection in mice.
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DOI：
10.1111/all.14241
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发表时间：
2020-08
期刊：
影响因子：
12.4
通讯作者：
Hershenson MB
中科院分区：
文献类型：
--
作者：
Han M;Ishikawa T;Bermick JR;Rajput C;Lei J;Goldsmith AM;Jarman CR;Lee J;Bentley JK;Hershenson MB
人鼻病毒（RV）的早期喘息相关呼吸道感染与哮喘的发生有关。6日龄未成熟小鼠的RV感染引起粘膜化生和气道高反应性，这与产生IL-13的2型先天淋巴细胞（ILC 2）的扩增相关，并依赖于IL-25和IL-33。我们研究了IL-1β对这种哮喘样表型的调节。6日龄野生型或NRLP 3 −/−小鼠接种假疫苗或RV-A1 B。选择的小鼠用IL-1受体拮抗剂（IL-1 RA）、抗IL-1β或重组IL-1β处理。RV感染诱导IL 25、IL 33、IL 4、IL 5、IL 13、muc 5ac和gob 5 mRNA表达、ILC 2扩增、粘液化生和气道高反应性。RV还诱导肺pro-IL-1β和NLRP 3的mRNA和蛋白表达以及caspase-1和pro-IL-1β的切割，表明炎性小体引发和激活。肺巨噬细胞是IL-1β的主要来源。用IL-1 RA、抗IL-1β或NLRP 3 KO抑制IL-1β信号传导增加RV诱导的2型细胞因子免疫应答、ILC 2数量和粘液化生，同时降低IL-17 mRNA表达。用IL-1β治疗具有相反的效果，降低IL-25、IL-33和粘膜化生，同时增加IL-17表达。IL-1β和IL-17分别抑制培养的气道上皮细胞中IL-25、IL-33和muc 5ac mRNA的表达。最后，与成熟小鼠相比，RV感染的6日龄小鼠显示IL-1β mRNA和蛋白表达降低。巨噬细胞IL-1β通过抑制上皮细胞固有细胞因子表达限制RV感染后的2型炎症和粘膜化生。未成熟动物中IL-1β产生的减少提供了允许在早期生命病毒感染后发生哮喘的机制。
Early-life wheezing-associated respiratory infection with human rhinovirus (RV) is associated with asthma development. RV infection of six day-old immature mice causes mucous metaplasia and airway hyperresponsiveness which is associated with the expansion of IL-13-producing type 2 innate lymphoid cells (ILC2s) and dependent on IL-25 and IL-33. We examined regulation of this asthma-like phenotype by IL-1β. Six day-old wild type or NRLP3−/− mice were inoculated with sham or RV-A1B. Selected mice were treated with IL-1 receptor antagonist (IL-1RA), anti-IL-1β or recombinant IL-1β. RV infection induced Il25, Il33, Il4, Il5, Il13, muc5ac and gob5 mRNA expression, ILC2 expansion, mucus metaplasia and airway hyperresponsiveness. RV also induced lung mRNA and protein expression of pro-IL-1β and NLRP3 as well as cleavage of caspase-1 and pro-IL-1β, indicating inflammasome priming and activation. Lung macrophages were a major source of IL-1β. Inhibition of IL-1β signaling with IL-1RA, anti-IL-1β or NLRP3 KO increased RV-induced type 2 cytokine immune responses, ILC2 number and mucus metaplasia, while decreasing IL-17 mRNA expression. Treatment with IL-1β had the opposite effect, decreasing IL-25, IL-33 and mucous metaplasia while increasing IL-17 expression. IL-1β and IL-17 each suppressed Il25, Il33 and muc5ac mRNA expression in cultured airway epithelial cells. Finally, RV-infected 6 day-old mice showed reduced IL-1β mRNA and protein expression compared to mature mice. Macrophage IL-1β limits type 2 inflammation and mucous metaplasia following RV infection by suppressing epithelial cell innate cytokine expression. Reduced IL-1β production in immature animals provides a mechanism permitting asthma development after early-life viral infection.
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影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
3.7
作者：
Piper SC;Ferguson J;Kay L;Parker LC;Sabroe I;Sleeman MA;Briend E;Finch DK
通讯作者：
Finch DK
DOI：
10.4049/jimmunol.1700216
发表时间：
2017-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Han M;Rajput C;Hong JY;Lei J;Hinde JL;Wu Q;Bentley JK;Hershenson MB
通讯作者：
Hershenson MB
影响因子：
30.5
作者：
Ohne, Yoichiro;Silver, Jonathan S.;Liu, Yong-Jun
通讯作者：
Liu, Yong-Jun
影响因子：
30.5
作者：
Bernink, Jochem H.;Ohne, Yoichiro;Humbles, Alison A.
通讯作者：
Humbles, Alison A.