Small extracellular vesicles derived from human mesenchymal stromal cells prevent group 2 innate lymphoid cell‐dominant allergic airway inflammation through delivery of miR‐146a‐5p

先天性淋巴细胞 间充质干细胞 过敏性炎症 微泡 外体 免疫学 炎症 细胞生物学 免疫系统 生物 胞外囊泡 间质细胞 医学 先天免疫系统 癌症研究 小RNA 基因 生物化学
作者
Shu-Bin Fang,Hongyu Zhang,Cong Wang,Bi‐Xin He,Xiaoqing Liu,Xiang-Ci Meng,Yaqi Peng,Zhibin Xu,Xingliang Fan,Zhang-Jin Wu,Chen Dong,Lei Zheng,Song Guo Zheng,Qing‐Ling Fu
出处
期刊:Journal of extracellular vesicles [Wiley]
卷期号:9 (1) 被引量:139
标识
DOI:10.1080/20013078.2020.1723260
摘要

Group 2 innate lymphoid cells (ILC2s) are recently reported to play a more critical role in allergic diseases. We previously identified that mesenchymal stromal cells (MSCs) elicited therapeutic effects on allergic airway inflammation. Small extracellular vesicles (sEV) derived from MSCs possess striking advantages including low immunogenicity and high biosafety, and is extremely promising cell-free therapeutic agents. However, the effects of MSC-sEV on ILC2s are still unclear. Additionally, scalable isolation protocols are required for the mass production of homogenous MSC-sEV especially in clinical application. We previously reported that induced pluripotent stem cells-derived MSCs were the ideal cellular source for the large preparation of MSC-sEV. Here we developed a standardized scalable protocol of anion-exchange chromatography for isolation of MSC-sEV, and investigated the effects of MSC-sEV on ILC2 function from patients with allergic rhinitis and in a mouse ILC2-dominant asthma model. The characterization of MSC-sEV was successfully demonstrated in terms of size, morphology and specific markers. Using flow cytometry and human Cytokine Antibody Array, MSC-sEV but not fibroblasts-sEV (Fb-sEV) were found to significantly inhibit the function of human ILC2s. Similarly, systemic administration of MSC-sEV but not Fb-sEV exhibited an inhibition of ILC2 levels, inflammatory cell infiltration and mucus production in the lung, a reduction in levels of T helper 2 cytokines, and alleviation of airway hyperresponsiveness in a mouse model of asthma. Using RNA sequencing, miR-146a-5p was selected as the candidate to mediate the above effects of MSC-sEV. We next revealed the uptake of ILC2s to MSC-sEV, and that transfer of miR-146a-5p in MSC-sEV to ILC2s in part contributed to the effects of MSC-sEV on ILC2s in vitro and in a mouse model. In conclusion, we demonstrated that MSC-sEV were able to prevent ILC2-dominant allergic airway inflammation at least partially through miR-146a-5p, suggesting that MSC-sEV could be a novel cell-free strategy for the treatment of allergic diseases.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
无奈柚子完成签到,获得积分10
刚刚
wan发布了新的文献求助10
1秒前
大模型应助笨笨的傲芙采纳,获得10
3秒前
I Think完成签到,获得积分10
4秒前
4秒前
山巅一寺一壶酒完成签到,获得积分10
7秒前
TTTaT完成签到,获得积分10
7秒前
8秒前
gzj完成签到,获得积分10
9秒前
端庄大白完成签到 ,获得积分10
10秒前
学疯发布了新的文献求助10
12秒前
梦之哆啦完成签到,获得积分10
14秒前
科研通AI2S应助zhangnan采纳,获得10
15秒前
15秒前
Swilder完成签到 ,获得积分10
17秒前
21秒前
小鹿5460发布了新的文献求助10
21秒前
charlotte3228发布了新的文献求助10
23秒前
乐乐应助可乐采纳,获得10
23秒前
爱幻想的青柠完成签到,获得积分20
24秒前
Ron完成签到,获得积分10
25秒前
大大大魔王喵帕斯完成签到,获得积分10
26秒前
威武白桃完成签到,获得积分20
27秒前
传奇3应助TAO采纳,获得10
27秒前
29秒前
29秒前
张子捷应助老白非采纳,获得10
29秒前
tiomooo完成签到,获得积分10
30秒前
31秒前
22鱼完成签到,获得积分10
32秒前
非常完成签到,获得积分10
32秒前
打打应助晾猫人采纳,获得10
34秒前
tzk完成签到,获得积分10
35秒前
Lili完成签到,获得积分10
37秒前
asd关闭了asd文献求助
37秒前
Zoe完成签到,获得积分10
38秒前
嗯哼应助家家采纳,获得10
39秒前
40秒前
香蕉觅云应助故意的篮球采纳,获得10
40秒前
qq完成签到 ,获得积分10
41秒前
高分求助中
The ACS Guide to Scholarly Communication 2500
Sustainability in Tides Chemistry 2000
Studien zur Ideengeschichte der Gesetzgebung 1000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Threaded Harmony: A Sustainable Approach to Fashion 810
Pharmacogenomics: Applications to Patient Care, Third Edition 800
Genera Insectorum: Mantodea, Fam. Mantidæ, Subfam. Hymenopodinæ (Classic Reprint) 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3082549
求助须知:如何正确求助?哪些是违规求助? 2735847
关于积分的说明 7539036
捐赠科研通 2385432
什么是DOI,文献DOI怎么找? 1264844
科研通“疑难数据库(出版商)”最低求助积分说明 612830
版权声明 597685