综述 REVIEW

乳外泌体对机体免疫调节作用的研究进展

  • 陈碧兰 ,
  • 黎梦 ,
  • 张永亮 ,
  • 陈婷
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  • 1. 华南农业大学动物科学学院, 国家生猪种业工程技术中心, 广东省动物营养调控重点实验室, 广州 510642;
    2. 嘉兴学院生物与化学工程学院, 嘉兴 314001
陈碧兰(1997—),女,广东韶关人,硕士,从事动物分子营养研究。E-mail:2339545310@qq.com

收稿日期: 2022-03-30

  网络出版日期: 2022-10-17

基金资助

国家自然科学基金项目(32072812,31802156,31872435);广东省自然科学基金面上项目(2019A1515011734,2021A1515011310)

Progress of Milk-Derived Exosomes on Immune Regulation

  • CHEN Bilan ,
  • LI Meng ,
  • ZHANG Yongliang ,
  • CHEN Ting
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  • 1. Guangdong Key Laboratory of Animal Nutrition Regulation, National Pig Breeding Engineering Technology Center, School of Animal Science, South China Agricultural University, Guangzhou 510642, China;
    2. School of Biology and Chemical Engineering, Jiaxing University, Jiaxing 314001, China

Received date: 2022-03-30

  Online published: 2022-10-17

摘要

外泌体(EVs)是直径为30~150 nm的细胞外磷脂双层囊泡,多种类型细胞、组织和生物液体均可分泌外泌体,包括血液、尿液、牛奶、眼泪和脑脊液等。母乳是哺乳动物生长发育不可替代的营养来源。除此之外,母乳喂养还能有效降低患病率,减少患各种疾病的风险,如坏死性小肠结肠炎(NEC)、肠胃炎、急性淋巴细胞白血病和急性髓系白血病等。母乳中富含乳铁蛋白、免疫球蛋白、生长因子、寡糖、多不饱和脂肪酸等生物活性成分,近年来还发现母乳中富含外泌体。有研究显示,乳外泌体(MEVs)具有一定的生物活性、miRNAs序列同源性和稳定性,可以直接被机体吸收并发挥免疫调节作用,本文着重对乳外泌体在炎症、肿瘤或通过直接或间接作用发挥免疫调节作用的研究进行综述,为丰富乳外泌体的生物学功能提供参考依据。

本文引用格式

陈碧兰 , 黎梦 , 张永亮 , 陈婷 . 乳外泌体对机体免疫调节作用的研究进展[J]. 动物营养学报, 2022 , 34(9) : 5543 -5551 . DOI: 10.3969/j.issn.1006-267x.2022.09.010

Abstract

Exosomes (EVs) are extracellular phospholipid bilayer vesicles with a diameter of 30 to 150 nm. It is reported that many types of cells, tissues and biological fluids can secrete exosomes, including blood, urine, milk, tears and cerebrospinal fluid. Breast milk is an irreplaceable nutrition for mammalian growth and development. In addition, breast feeding can reduce morbidity and the risk of infected various diseases, such as necrotizing enterocolitis (NEC), gastroenteritis, acute lymphoblastic leukemia and acute lymphoblastic leukemia, etc. Breast milk is rich in various bioactive components, such as lactoferrin, immunoglobulins, growth factors, oligosaccharides and polyunsaturated fatty acids. In recent years, it has been found that breast milk is rich in exosomes. It is reported that milk-derived exosomes (MEVs) have certain biological activity, miRNAs sequence homology and stability, and can be absorbed by different cells directly, and then play an immunity regulatory role in organism. This review summarizes the milk-derived exosome' function of inflammation and tumors, and their directly or indirectly role in immunomodulatory, which will provide a reference for enriching the biological functions of milk-derived exosomes.

参考文献

[1] MATHIVANAN S, JI H, SIMPSON R J.Exosomes:extracellular organelles important in intercellular communication[J].Journal of Proteomics, 2010, 73(10):1907-1920.  
[2] VAN DER POL E, BÖING A N, HARRISON P, et al.Classification, functions, and clinical relevance of extracellular vesicles[J].Pharmacological Reviews, 2012, 64(3):676-705.  
[3] BANG C, THUM T.Exosomes:new players in cell-cell communication[J].The International Journal of Biochemistry & Cell Biology, 2012, 44(11):2060-2064.  
[4] VAN DONGEN H M, MASOUMI N, WITWER K W, et al.Extracellular vesicles exploit viral entry routes for cargo delivery[J].Microbiology and Molecular Biology Reviews, 2016, 80(2):369-386.  
[5] ADMYRE C, JOHANSSON S M, QAZI K R, et al.Exosomes with immune modulatory features are present in human breast milk[J].Journal of Immunology, 2007, 179(3):1969-1978.  
[6] FENG X, CHEN X L, ZHENG X C, et al.Latest trend of milk derived exosomes:cargos, functions, and applications[J].Frontiers in Nutrition, 2021, 8:747294.
[7] ZEMPLENI J, SUKREET S, ZHOU F, et al.Milk-derived exosomes and metabolic regulation[J].Annual Review of Animal Biosciences, 2019, 7:245-262.
[8] SAMUEL M, CHISANGA D, LIEM M, et al.Bovine milk-derived exosomes from colostrum are enriched with proteins implicated in immune response and growth[J].Scientific Reports, 2017, 7(1):5933.
[9] MUNAGALA R, AQIL F, JEYABALAN J, et al.Bovine milk-derived exosomes for drug delivery[J].Cancer Letters, 2016, 371(1):48-61.  
[10] AGRAWAL A K, AQIL F, JEYABALAN J, et al.Milk-derived exosomes for oral delivery of paclitaxel[J].Nanomedicine-Nanotechnology Biology and Medicine, 2017, 13(5):1627-1636.  
[11] LI S Y, TANG Y, DOU Y S.The potential of milk-derived exosomes for drug delivery[J].Current Drug Delivery, 2021, 18(6):688-699.  
[12] BHAT A A, UPPADA S, ACHKAR I W, et al.Tight junction proteins and signaling pathways in cancer and inflammation:a functional crosstalk[J].Frontiers in Physiology, 2019, 9:1942.
[13] KIM K U, KIM W H, JEONG C H, et al.More than nutrition:therapeutic potential of breast milk-derived exosomes in cancer[J].International Journal of Molecular Sciences, 2020, 21(19):7327.
[14] CHEN W Y, WANG R, LI D, et al.Comprehensive analysis of the glycome and glycoproteome of bovine milk-derived exosomes[J].Journal of Agricultural and Food Chemistry, 2020, 68(45):12692-12701.  
[15] BENMOUSSA A, LAUGIER J, BEAUPARLANT C J, et al.Complexity of the microRNA transcriptome of cow milk and milk-derived extracellular vesicles isolated via differential ultracentrifugation[J].Journal of Dairy Science, 2020, 103(1):16-29.  
[16] BENMOUSSA A, LY S, SHAN S T, et al.A subset of extracellular vesicles carries the bulk of microRNAs in commercial dairy cow's milk[J].Journal of Extracellular Vesicles, 2017, 6(1):1401897.
[17] LIAO Y L, DU X G, LI J, et al.Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells[J].Molecular Nutrition & Food Research, 2017, 61(11):1700082.
[18] ORTEGA-ANAYA J, JIMÉNEZ-FLORES R.Symposium review:the relevance of bovine milk phospholipids in human nutrition-evidence of the effect on infant gut and brain development[J].Journal of Dairy Science, 2019, 102(3):2738-2748.  
[19] REIF S, ELBAUM-SHIFF Y, KOROUKHOV N, et al.Cow and human milk-derived exosomes ameliorate colitis in DSS murine model[J].Nutrients, 2020, 12(9):2589.
[20] ALSAWEED M, HARTMANN P E, GEDDES D T, et al.MicroRNAs in breastmilk and the lactating breast:potential immunoprotectors and developmental regulators for the infant and the mother[J].International Journal of Environmental Research and Public Health, 2015, 12(11):13981-14020.  
[21] CUI J, ZHOU B Y, ROSS S A, et al.Nutrition, microRNAs, and human health[J].Advances in Nutrition, 2017, 8(1):105-112.  
[22] QIN W Y, TSUKASAKI Y, DASGUPTA S, et al.Exosomes in human breast milk promote EMT[J].Clinical Cancer Research, 2016, 22(17):4517-4524.  
[23] PIETERS B C H, ARNTZ O J, BENNINK M B, et al.Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-β[J].PLoS One, 2015, 10(3):e0121123.
[24] GOLAN-GERSTL R, ELBAUM SHIFF Y, MOSHAYOFF V, et al.Characterization and biological function of milk-derived miRNAs[J].Molecular Nutrition & Food Research, 2017, 61(10):1700009.
[25] VAN HERWIJNEN M J C, DRIEDONKS T A P, SNOEK B L, et al.Abundantly present miRNAs in milk-derived extracellular vesicles are conserved between mammals[J].Frontiers in Nutrition, 2018, 5:81.
[26] WOLF T, BAIER S R, ZEMPLENI J.The intestinal transport of bovine milk exosomes is mediated by endocytosis in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 cells[J].The Journal of Nutrition, 2015, 145(10):2201-2206.  
[27] BAIER S R, NGUYEN C, XIE F, et al.MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers[J].The Journal of Nutrition, 2014, 144(10):1495-1500.  
[28] KOSAKA N, IZUMI H, SEKINE K, et al.microRNA as a new immune-regulatory agent in breast milk[J].Silence, 2010, 1(1):7.
[29] MUNIR J, LEE M, RYU S.Exosomes in food:health benefits and clinical relevance in diseases[J].Advances in Nutrition, 2020, 11(3):687-696.  
[30] ZONNEVELD M I, BRISSON A R, VAN HERWIJNEN M J C, et al.Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures[J].Journal of Extracellular Vesicles, 2014, 3(1):24215.
[31] ZHAO Z H, YU S R, XU M J, et al.Effects of microwave on extracellular vesicles and microRNA in milk[J].Journal of Dairy Science, 2018, 101(4):2932-2940.  
[32] HOWARD K M, JATI KUSUMA R, BAIER S R, et al.Loss of miRNAs during processing and storage of cow's (Bos taurus) milk[J].Journal of Agricultural and Food Chemistry, 2015, 63(2):588-592.  
[33] KLEINJAN M, VAN HERWIJNEN M J, LIBREGTS S F, et al.Regular industrial processing of bovine milk impacts the integrity and molecular composition of extracellular vesicles[J].The Journal of Nutrition, 2021, 151(6):1416-1425.  
[34] KIRCHNER B, PFAFFL M W, DUMPLER J, et al.MicroRNA in native and processed cow's milk and its implication for the farm milk effect on asthma[J].The Journal of Allergy and Clinical Immunology, 2016, 137(6):1893-1895.e13.  
[35] VLASSOV A V, MAGDALENO S, SETTERQUIST R, et al.Exosomes:current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials[J].Biochimica et Biophysica Acta, 2012, 1820(7):940-948.  
[36] LAI R C, ARSLAN F, LEE M M, et al.Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury[J].Stem Cell Research, 2010, 4(3):214-222.  
[37] WANG K, ZHANG S L, WEBER J, et al.Export of microRNAs and microRNA-protective protein by mammalian cells[J].Nucleic Acids Research, 2010, 38(20):7248-7259.  
[38] ZONNEVELD M I, VAN HERWIJNEN M J C, FERNANDEZ-GUTIERREZ M M, et al.Human milk extracellular vesicles target nodes in interconnected signaling pathways that enhance oral epithelial barrier function and dampen immune responses[J].Journal of Extracellular Vesicles, 2021, 10(5):e12071.
[39] RAHMAN M M, SHIMIZU K, YAMAUCHI M, et al.Acidification effects on isolation of extracellular vesicles from bovine milk[J].PLoS One, 2019, 14(9):e0222613.
[40] BENMOUSSA A, MICHEL S, GILBERT C, et al.Isolating multiple extracellular vesicles subsets, including exosomes and membrane vesicles, from bovine milk using sodium citrate and differential ultracentrifugation[J].Bio-Protocol, 2020, 10(11):e3636.
[41] WIJENAYAKE S, EISHA S, TAWHIDI Z, et al.Comparison of methods for pre-processing, exosome isolation, and RNA extraction in unpasteurized bovine and human milk[J].PLoS One, 2021, 16(9):e0257633.
[42] XIANG X C, GUAN F L, JIAO F L, et al.A new urinary exosome enrichment method by a combination of ultrafiltration and TiO2 nanoparticles[J].Analytical Methods, 2021, 13(13):1591-1600.  
[43] NATA T, FUJIYA M, UENO N, et al.MicroRNA-146b improves intestinal injury in mouse colitis by activating nuclear factor-κB and improving epithelial barrier function[J].Journal of Gene Medicine, 2013, 15(6/7):249-260.
[44] COLOMBO M, RAPOSO G, THÉRY C.Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles[J].Annual Review of Cell and Developmental Biology, 2014, 30:255-289.
[45] JADLI A S, BALLASY N, EDALAT P, et al.Inside (sight) of tiny communicator:exosome biogenesis, secretion, and uptake[J].Molecular and Cellular Biochemistry, 2020, 467(1):77-94.
[46] SHANDILYA S, RANI P, ONTERU S K, et al.Natural ligand-receptor mediated loading of siRNA in milk derived exosomes[J].Journal of Biotechnology, 2020, 318:1-9.
[47] ABELS E R, BREAKEFIELD X O.Introduction to extracellular vesicles:biogenesis, RNA cargo selection, content, release, and uptake[J].Cellular and Molecular Neurobiology, 2016, 36(3):301-312.  
[48] YUN B, MABURUTSE B E, KANG M, et al.Short communication:dietary bovine milk-derived exosomes improve bone health in an osteoporosis-induced mouse model[J].Journal of Dairy Science, 2020, 103(9):7752-7760.  
[49] GAO R N, ZHANG R, QIAN T, et al.A comparison of exosomes derived from different periods breast milk on protecting against intestinal organoid injury[J].Pediatric Surgery International, 2019, 35(12):1363-1368.  
[50] HE S, LIU G, ZHU X P.Human breast milk-derived exosomes may help maintain intestinal epithelial barrier integrity[J].Pediatric Research, 2021, 90(2):366-372.  
[51] STREMMEL W, WEISKIRCHEN R, MELNIK B C.Milk exosomes prevent intestinal inflammation in a genetic mouse model of ulcerative colitis:a pilot experiment[J].Inflammatory Intestinal Diseases, 2020, 5(3):117-123.  
[52] BADAWY A A, EL-MAGD M A, ALSADRAH S A.Therapeutic effect of camel milk and its exosomes on MCF7 cells in vitro and in vivo[J].Integrative Cancer Therapies, 2018, 17(4):1235-1246.  
[53] GAO H N, GUO H Y, ZHANG H, et al.Yak-milk-derived exosomes promote proliferation of intestinal epithelial cells in an hypoxic environment[J].Journal of Dairy Science, 2019, 102(2):985-996.  
[54] LI B, HOCK A, WU R Y, et al.Bovine milk-derived exosomes enhance goblet cell activity and prevent the development of experimental necrotizing enterocolitis[J].PLoS One, 2019, 14(1):e0211431.
[55] MEDZHITOV R.Origin and physiological roles of inflammation[J].Nature, 2008, 454(7203):428-435.  
[56] KARIN M, CLEVERS H.Reparative inflammation takes charge of tissue regeneration[J].Nature, 2016, 529(7586):307-315.  
[57] MCCOMB S, THIRIOT A, AKACHE B, et al.Introduction to the immune system[J].Methods in Molecular Biology, 2019, 2024:1-24.
[58] PIETERS B C H, ARNTZ O J, AARTS J, et al.Bovine milk-derived extracellular vesicles inhibit catabolic and inflammatory processes in cartilage from osteoarthritis patients[J].Molecular Nutrition & Food Research, 2022, 66(6):e2100764.
[59] GOOD M, SODHI C P, EGAN C E, et al.Breast milk protects against the development of necrotizing enterocolitis through inhibition of Toll-like receptor 4 in the intestinal epithelium via activation of the epidermal growth factor receptor[J].Mucosal Immunology, 2015, 8(5):1166-1179.  
[60] KAHN S, LIAO Y L, DU X G, et al.Exosomal microRNAs in milk from mothers delivering preterm infants survive in vitro digestion and are taken up by human intestinal cells[J].Molecular Nutrition & Food Research, 2018, 62(11):e1701050.
[61] RICH B S, DOLGIN S E.Necrotizing enterocolitis[J].Pediatrics in Review, 2017, 38(12):552-559.  
[62] LANDSKRON G, DE LA FUENTE M, THUWAJIT P, et al.Chronic inflammation and cytokines in the tumor microenvironment[J].Journal of Immunology Research, 2014, 2014:149185.
[63] REIF S, ELBAUM SHIFF Y, GOLAN-GERSTL R.Milk-derived exosomes (MDEs) have a different biological effect on normal fetal colon epithelial cells compared to colon tumor cells in a miRNA-dependent manner[J].Journal of Translational Medicine, 2019, 17(1):325.
[64] DAS L M, TORRES-CASTILLO M D L A, GILL T, et al.TGF-β conditions intestinal T cells to express increased levels of miR-155, associated with down-regulation of IL-2 and itk mRNA[J].Mucosal Immunology, 2013, 6(1):167-176.  
[65] MELNIK B C, SCHMITZ G.Exosomes of pasteurized milk:potential pathogens of Western diseases[J].Journal of Translational Medicine, 2019, 17(1):3.
[66] AQIL F, MUNAGALA R, JEYABALAN J, et al.Milk exosomes-natural nanoparticles for siRNA delivery[J].Cancer Letters, 2019, 449:186-195.
[67] SEDYKH S, KULESHOVA A, NEVINSKY G.Milk exosomes:perspective agents for anticancer drug delivery[J].International Journal of Molecular Sciences, 2020, 21(18):6646.
[68] QUINTANA-HAYASHI M P, PADRA M, PADRA J T, et al.Mucus-pathogen interactions in the gastrointestinal tract of farmed animals[J].Microorganisms, 2018, 6(2):55.
[69] YOO B B, MAZMANIAN S K.The enteric network:interactions between the immune and nervous systems of the gut[J].Immunity, 2017, 46(6):910-926.  
[70] XIE M Y, CHEN T, XI Q Y, et al.Porcine milk exosome miRNAs protect intestinal epithelial cells against deoxynivalenol-induced damage[J].Biochemical Pharmacology, 2020, 175:113898.
[71] XIE M Y, HOU L J, SUN J J, et al.Porcine milk exosome miRNAs attenuate LPS-induced apoptosis through inhibiting TLR4/NF-κB and p53 pathways in intestinal epithelial cells[J].Journal of Agricultural and Food Chemistry, 2019, 67(34):9477-9491.  
[72] CHEN Y, XIAO Y, GE W, et al.miR-200b inhibits TGF-β1-induced epithelial-mesenchymal transition and promotes growth of intestinal epithelial cells[J].Cell Death & Disease, 2013, 4(3):e541.
[73] HAUPT Y, MAYA R, KAZAZ A, et al.Mdm2 promotes the rapid degradation of p53[J].Nature, 1997, 387(6630):296-299.  
[74] BARTEL D P.MicroRNAs:target recognition and regulatory functions[J].Cell, 2009, 136(2):215-233.  
[75] MELNIK B C.Milk disrupts p53 and DNMT1, the guardians of the genome:implications for acne vulgaris and prostate cancer[J].Nutrition & Metabolism, 2017, 14:55.
[76] ZENG B, CHEN T, LUO J Y, et al.Biological characteristics and roles of noncoding RNAs in milk-derived extracellular vesicles[J].Advances in Nutrition, 2021, 12(3):1006-1019.  
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