Porcine Milk-Derived Small Extracellular Vesicles Promote Intestinal Immunoglobulin Production through pIgR.
Porcine Milk-Derived Small Extracellular Vesicles Promote Intestinal Immunoglobulin Production through pIgR.
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猪乳来源的小细胞外囊泡通过 pIgR 促进肠道免疫球蛋白的产生
DOI：
10.3390/ani11061522
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发表时间：
2021-05-24
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Zeng B;Wang H;Luo J;Xie M;Zhao Z;Chen X;Wang D;Sun J;Xi Q;Chen T;Zhang Y
乳汁作为幼龄哺乳动物不可替代的营养来源，具有多种生物学功能。乳源性细胞外囊泡是最近发现的牛奶成分，对肠道健康和免疫有潜在的调节作用。本研究通过体内和体外实验研究了猪乳小细胞外囊泡（PM-sEVs）对肠道免疫的影响。结果表明，pm - sev可促进小鼠和仔猪肠道分泌性免疫球蛋白a （SIgA）水平，并增加聚合免疫球蛋白受体（pIgR）的表达水平。我们发现pm - sev中的circ-XPO4是一个至关重要的circRNA，它通过抑制肠细胞中miR-221-5p来促进pIgR的表达。综上所述，本研究为猪乳在肠道免疫中的营养生理提供了新的认识。分泌性免疫球蛋白A （SIgA）在肠道获得性免疫和粘膜稳态中起重要作用。母乳是哺乳动物出生后不可替代的营养来源。目前的研究表明，乳源性小细胞外囊泡（sev）及其rna货物在肠道健康和免疫调节中的潜在功能作用。然而，缺乏研究证明乳源性sev如何影响受体肠道免疫。本研究通过体内实验发现，猪乳小细胞外囊泡（PM-sEVs）能促进小鼠和仔猪肠道SIgA水平，提高聚合免疫球蛋白受体（pIgR）的表达水平。我们利用猪小肠上皮细胞系（IPEC-J2）研究了PM-sEVs在体外提高pIgR表达水平的机制。通过生物信息学分析、双荧光素酶报告基因检测以及相应非编码rna的过表达或敲低，我们发现pm - sev中的circ-XPO4是一个至关重要的circRNA，它通过抑制miR-221-5p在肠细胞中导致pIgR的表达。重要的是，我们还观察到口服pm - sev增加了仔猪小肠中circ-XPO4的水平，降低了miR-221-5p的水平，这表明乳源性sev中的circrna充当了受体mirna的海绵。本研究首次揭示了pm - sev能够通过向受体传递circrna并海绵化受体的原始mirna来刺激肠道SIgA的产生，也为深入了解动物奶sev在肠道免疫中的作用和机制提供了有价值的数据。
Simple Summary As the irreplaceable nutrient source for young mammals, milk has a number of biological functions. Milk derived extracellular vesicles are a recently discovered component of milk and have potential regulatory effects on intestinal health and immunity. In this study, in vivo and in vitro experiments were performed to examine the effects of porcine milk small extracellular vesicles (PM-sEVs) on intestinal immunity. As a result, PM-sEVs promoted intestinal secretory immunoglobulin A (SIgA) levels, and increased the expression levels of the polymeric immunoglobulin receptor (pIgR) both in mice and piglet. We identified circ-XPO4 in PM-sEVs as a crucial circRNA, which promotes the expression of pIgR via the suppression of miR-221-5p in the intestinal cell. In conclusion, our research provides a new understanding of the nutritional physiology of porcine milk in intestinal immunity. Abstract Secretory immunoglobulin A (SIgA) plays an important role in gut acquired immunity and mucosal homeostasis. Breast milk is the irreplaceable nutritional source for mammals after birth. Current studies have shown the potential functional role of milk-derived small extracellular vesicles (sEVs) and their RNAs cargo in intestinal health and immune regulation. However, there is a lack of studies to demonstrate how milk-derived sEVs affect intestinal immunity in recipient. In this study, through in vivo experiments, we found that porcine milk small extracellular vesicles (PM-sEVs) promoted intestinal SIgA levels, and increased the expression levels of polymeric immunoglobulin receptor (pIgR) both in mice and piglet. We examined the mechanism of how PM-sEVs increased the expression level of pIgR in vitro by using a porcine small intestine epithelial cell line (IPEC-J2). Through bioinformatics analysis, dual-luciferase reporter assays, and overexpression or knockdown of the corresponding non-coding RNAs, we identified circ-XPO4 in PM-sEVs as a crucial circRNA, which leads to the expression of pIgR via the suppression of miR-221-5p in intestinal cells. Importantly, we also observed that oral administration of PM-sEVs increased the level of circ-XPO4 and decreased the level of miR-221-5p in small intestine of piglets, indicating that circRNAs in milk-derived sEVs act as sponge for miRNAs in recipients. This study, for the first time, reveals that PM-sEVs have a capacity to stimulate intestinal SIgA production by delivering circRNAs to receptors and sponging the recipient’s original miRNAs, and also provides valuable data for insight into the role and mechanism of animal milk sEVs in intestinal immunity.
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影响因子：
2.6
作者：
Chen T;Xi QY;Sun JJ;Ye RS;Cheng X;Sun RP;Wang SB;Shu G;Wang LN;Zhu XT;Jiang QY;Zhang YL
通讯作者：
Zhang YL
影响因子：
9.3
作者：
O'Reilly, Daniel;Dorodnykh, Denis;Munblit, Daniel
通讯作者：
Munblit, Daniel
影响因子：
3.2
作者：
Martin C;Patel M;Williams S;Arora H;Brawner K;Sims B
通讯作者：
Sims B
猪乳外泌体中 microRNA 的探索
影响因子：
4.4
作者：
Chen T;Xi QY;Ye RS;Cheng X;Qi QE;Wang SB;Shu G;Wang LN;Zhu XT;Jiang QY;Zhang YL
通讯作者：
Zhang YL
影响因子：
8
作者：
通讯作者：
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