3,310
Views
3
CrossRef citations to date
0
Altmetric
Review

Extracellular vesicles regulate immune responses and cellular function in intestinal inflammation and repair

, &
Article: e1431038 | Received 28 Nov 2017, Accepted 13 Jan 2018, Published online: 09 Feb 2018

References

  • Xavier RJ, Podolsky DK. Unraveling the pathogenesis of inflammatory bowel disease. Nat. 2007;448(7152):427–34. doi:10.1038/nature06005. PMID:17653185.
  • Xu X, Liu C, Liu Z. Dysregulation of mucosal immune response in pathogenesis of inflammatory bowel disease. World J Gastroenterol. 2014;20(12):3255–64. doi:10.3748/wjg.v20.i12.3255. PMID:24695798.
  • Vrakas S, Mountzouris KC, Michalopoulos G, Karamanolis G, Papatheodoridis G, Tzathas C, Gazouli M. Intestinal bacteria composition and translocation of bacteria in inflammatory bowel disease. Plos One. 2017;12(1):e0170034. doi:10.1371/journal.pone.0170034. PMID:28099495.
  • Sumagin R, Robin AZ, Nusrat A, Parkos CA. Activation of PKCβII by PMA facilitates enhanced epithelial wound repair through increased cell spreading and migration. PLoS ONE. 2013;8(2):e55775. doi:10.1371/journal.pone.0055775. PMID:23409039.
  • Leoni G, Neumann P, Sumagin R, Denning TL, Nusrat A. Wound repair: role of immune–epithelial interactions. Mucosal Immunol. 2015;8(5):959–68. doi:10.1038/mi.2015.63. PMID:26174765.
  • Chao LH, Murray MM. The role of inflammation and blood cells in wound healing. The ACL Handb. 2013;7(6):73–89. doi:10.1007/978-1-4614-0760-7_6.
  • Hoang AN, Jones CN, Dimisko L, Hamza B, Martel J, Kojic N, Irimia D. Measuring neutrophil speed and directionality during chemotaxis, directly from a droplet of whole blood. Technology. 2013;01(01):49–57. doi:10.1142/s2339547813500040.
  • Jones CN, Hoang AN, Dimisko L, Hamza B, Martel J, Irimia D. Microfluidic platform for measuring neutrophil chemotaxis from unprocessed whole blood. J Visualized Exp. 2014;88(1):1–6. doi:10.3791/51215.
  • Leliefeld PH, Wessels CM, Leenen LP, Koenderman L, Pillay J. The role of neutrophils in immune dysfunction during severe inflammation. Crit Care. 2016;20(1):73. doi:10.1186/s13054-016-1250-4. PMID:27005275.
  • Segal AW. How neutrophils kill microbes. Annu Rev Immunol. 2005;23(1):197–223. doi:10.1146/annurev.immunol.23.021704.115653. PMID:15771570.
  • Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126–67. doi:10.1089/ars.2012.5149. PMID:23991888.
  • Perobelli S, Galvani R, Gonçalves-Silva T, Xavier C, Nóbrega A, Bonomo A. Plasticity of neutrophils reveals modulatory capacity. Brazilian J Med Biol Res. 2015;48(8):665–75. doi:10.1590/1414-431x20154524.
  • Mariano F, Campanelli A, Mattos-Graner R, Gonçalves R. Antimicrobial peptides and nitric oxide production by neutrophils from periodontitis subjects. Brazilian J Med Biol Res. 2012;45(11):1017–24. doi:10.1590/s0100-879x2012007500123.
  • Kebir DE, Gjorstrup P, Filep JG. Resolvin E1 promotes phagocytosis-induced neutrophil apoptosis and accelerates resolution of pulmonary inflammation. Proc Natl Acad Sci. 2012;109(37):14983–8. doi:10.1073/pnas.1206641109. PMID:22927428.
  • Brook M, Tomlinson GH, Miles K, Smith RW, Rossi AG, Hiemstra PS, Gray M. Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation. Proc Natl Acad Sci. 2016;113(16):4350–5. doi:10.1073/pnas.1601831113. PMID:27044108.
  • Alalwani M, Sierigk J, Bals R. The antimicrobial peptide LL-37 modulates the inflammatory and host defense response of human neutrophils. Eur J Immunol. 2010;40(4):1118–1126. doi:10.1002/eji.200939275.
  • Tsuji S, Taniuchi S, Hasui M, Yamamoto A, Kobayashi Y. Increased nitric oxide production by neutrophils from patients with chronic granulomatous disease on trimethoprim–sulfamethoxazole. Nitric Oxide. 2002;7(4):283–8. doi:10.1016/s1089-8603(02)00110-6. PMID:12446177.
  • Grotendorst GR, Smale G, Pencev D. Production of transforming growth factor beta by human peripheral blood monocytes and neutrophils. J Cell Physiol. 1989;140(2):396–402. doi:10.1002/jcp.1041400226. PMID:2745570.
  • Leoni G, Neumann P, Kamaly N, Quiros M, Nishio H, Jones HR, Nusrat A. Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest. 2015;125(3):1215–27. doi:10.1172/jci76693. PMID:25664854.
  • Sumagin R, Brazil JC, Nava P, Nishio H, Alam A, Luissint AC, Parkos CA. Neutrophil interactions with epithelial-expressed ICAM-1 enhances intestinal mucosal wound healing. Mucosal Immunol. 2016;9(5):1151–62. doi:10.1038/mi.2015.135. PMID:26732677.
  • Nusrat A, Parkos C, Liang T, Carnes D, Madara J. Neutrophil migration across model intestinal epithelia: Monolayer disruption and subsequent events in epithelial repair. Gastroenterology. 1997;113(5):1489–500. doi:10.1053/gast.1997.v113.pm9352851. PMID:9352851.
  • Lech M, Anders H. Macrophages and fibrosis: how resident and infiltrating mononuclear phagocytes orchestrate all phases of tissue injury and repair. Biochim Biophys Acta (BBA) – Mol Basis Dis. 2013;1832(7):989–97. doi:10.1016/j.bbadis.2012.12.001.
  • Novak ML, Koh TJ. Phenotypic transitions of macrophages orchestrate tissue repair. Am J Pathol. 2013;183(5):1352–63. doi:10.1016/j.ajpath.2013.06.034 PMID:24091222.
  • Yamada A, Arakaki R, Saito M, Ishimaru N. Role of regulatory T cell in the pathogenesis of inflammatory bowel disease. World J Gastroenterol. 2016;22(7):2195–205. doi:10.3748/wjg.v22.i7.2195 PMID:26900284.
  • Buzas EI, György B, Nagy G, Falus A, Gay S. Emerging role of extracellular vesicles in inflammatory diseases. Nat Rev Rheumatol. 2014;10(6):356–64. doi:10.1038/nrrheum.2014.19. PMID:24535546.
  • Cicero AL, Stahl PD, Raposo G. Extracellular vesicles shuffling intercellular messages: for good or for bad. Curr Opin Cell Biol. 2015;35:69–77. doi:10.1016/j.ceb.2015.04.013. PMID:26001269.
  • Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30(1):255–89. doi:10.1146/annurev-cellbio-101512-122326. PMID:25288114.
  • Al-Nedawi K, Mian MF, Hossain N, Karimi K, Mao Y, Forsythe P, Bienenstock J. Gut commensal microvesicles reproduce parent bacterial signals to host immune and enteric nervous systems. FASEB J. 2014;29(2):684–95. doi:10.1096/fj.14-259721. PMID:25392266.
  • Niel GV, Raposo G, Candalh C, Boussac M, Hershberg R, Cerf–Bensussan N, Heyman M. Intestinal epithelial cells secrete exosome–like vesicles. Gastroenterology. 2001;121(2):337–49. doi:10.1053/gast.2001.26263. PMID:11487543.
  • Yamamoto S, Niida S, Azuma E, Yanagibashi T, Muramatsu M, Huang TT, Sasahara M. Inflammation-induced endothelial cell-derived extracellular vesicles modulate the cellular status of pericytes. Sci Rep. 2015;5(1):8505. doi:10.1038/srep08505.
  • Robbins PD, Morelli AE. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol. 2014;14(3):195–208. doi:10.1038/nri3622. PMID:24566916.
  • Kastelowitz N, Yin H. Exosomes and microvesicles: identification and targeting by particle size and lipid chemical probes. Chem Bio Chem. 2014;15(7):923–8. doi:10.1002/cbic.201400043. PMID:24740901.
  • Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–83. doi:10.1083/jcb.201211138. PMID:23420871.
  • Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 2017;75(2):193–208. doi:10.1007/s00018-017-2595-9. PMID:28733901.
  • Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Théry C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci. 2016;113(8):968–77. doi:10.1073/pnas.1521230113.
  • Durcin M, Fleury A, Taillebois E, Hilairet G, Krupova Z, Henry C, Lay SL. Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles. J Extracell Vesicles. 2017;6(1):1305677. doi:10.1080/20013078.2017.1305677. PMID:28473884.
  • Abels E, Breakefield X. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol. 2016;36(3):301–12. doi:10.1007/s10571-016-0366-z. PMID:27053351.
  • Liu Y, Lu Q. Extracellular vesicle microRNAs: biomarker discovery in various diseases based on RT-qPCR. Biomarkers Med. 2015;9(8):791–805. doi:10.2217/bmm.15.45.
  • Moldovan L, Batte K, Wang Y, Wisler J, Piper M. Analyzing the circulating MicroRNAs in exosomes/extracellular vesicles from Serum or Plasma by qRT-PCR. Methods Mol Biol Circulating MicroRNAs. 2013;1024:129–45. doi:10.1007/978-1-62703-453-1_10.
  • Zhang J, Li S, Li L, Li M, Guo C, Yao J, Mi S. Exosome and exosomal MicroRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics. 2015;13(1):17–24. doi:10.1016/j.gpb.2015.02.001. PMID:25724326.
  • Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res. 2011;39(16):7223–33. doi:10.1093/nar/gkr254. PMID:21609964.
  • Dalli J, Montero-Melendez T, Norling LV, Yin X, Hinds C, Haskard D, Perretti M. Heterogeneity in neutrophil microparticles reveals distinct proteome and functional properties. Mol Cell Proteomics. 2013;12(8):2205–19. doi:10.1074/mcp.m113.028589. PMID:23660474.
  • Perez-Pujol S, Marker PH, Key NS. Platelet microparticles are heterogeneous and highly dependent on the activation mechanism: Studies using a new digital flow cytometer. Cytometry Part A. 2007;71A(1):38–45. doi:10.1002/cyto.a.20354.
  • Kalra H, Drummen G, Mathivanan S. Focus on extracellular vesicles: introducing the next small big thing. Int J Mol Sci. 2016;17(2):170. doi:10.3390/ijms17020170. PMID:26861301.
  • Frey B, Gaipl US. The immune functions of phosphatidylserine in membranes of dying cells and microvesicles. Semin Immunopathol. 2010;33(5):497–516. doi:10.1007/s00281-010-0228-6. PMID:20941495.
  • Liu M, Reilly MP, Casasanto P, Mckenzie SE, Williams KJ. Cholesterol enrichment of human monocyte/macrophages induces surface exposure of phosphatidylserine and the release of biologically-active tissue factor-positive microvesicles. Arterioscler Thromb Vasc Biol. 2006;27(2):430–5. doi:10.1161/01.atv.0000254674.47693.e8. PMID:17158353.
  • Fernández-Messina L, Gutiérrez-Vázquez C, Rivas-García E, Sánchez-Madrid F, Fuente HD. Immunomodulatory role of microRNAs transferred by extracellular vesicles. Biol Cell. 2015;107(3):61–77. doi:10.1111/boc.201400081. PMID:25564937.
  • Robbins PD, Dorronsoro A, Booker CN. Regulation of chronic inflammatory and immune processes by extracellular vesicles. J Clin Invest. 2016;126(4):1173–80. doi:10.1172/jci81131. PMID:27035808.
  • Butin-Israeli V, Houser MC, Feng M, Thorp EB, Nusrat A, Parkos CA, Sumagin R. Deposition of microparticles by neutrophils onto inflamed epithelium: a new mechanism to disrupt epithelial intercellular adhesions and promote transepithelial migration. FASEB J. 2016;30(12):4007–20. doi:10.1096/fj.201600734r. PMID:27553226.
  • Helwa I, Cai J, Drewry MD, Zimmerman A, Dinkins MB, Khaled ML, Liu Y. A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. Plos One. 2017;12(1):e0170628. doi:10.1371/journal.pone.0170628. PMID:28114422.
  • Palanisamy V, Sharma S, Deshpande A, Zhou H, Gimzewski J, Wong DT. Nanostructural and transcriptomic analyses of human saliva derived exosomes. PLoS ONE. 2010;5(1):e8577. doi:10.1371/journal.pone.0008577. PMID:20052414.
  • Lv L, Cao Y, Liu D, Xu M, Liu H, Tang R, Liu B. Isolation and Quantification of MicroRNAs from urinary exosomes/microvesicles for biomarker discovery. Int J Biol Sci. 2013;9(10):1021–31. doi:10.7150/ijbs.6100. PMID:24250247.
  • Mitsuhashi S, Feldbrügge L, Csizmadia E, Mitsuhashi M, Robson SC, Moss AC. Luminal extracellular vesicles (EVs) in inflammatory bowel disease (IBD) exhibit proinflammatory effects on epithelial cells and macrophages. Inflamm Bowel Dis. 2016;22(7):1587–95. doi:10.1097/mib.0000000000000840. PMID:27271497.
  • Schwab A, Meyering SS, Lepene B, Iordanskiy S, Hoek ML, Hakami RM, Kashanchi F. Extracellular vesicles from infected cells: potential for direct pathogenesis. Front Microbiol. 2015;6:1132. doi:10.3389/fmicb.2015.01132.
  • Mi S, Zhang J, Zhang W, Huang RS. Circulating MicroRNAs as biomarkers for inflammatory diseases. MicroRNA. 2013;2(1):64–72. doi:10.2174/2211536611302010007.
  • Headland SE, Jones HR, Norling LV, Kim A, Souza PR, Corsiero E, Perretti M. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci Transl Med. 2015;7(315):e315. doi:10.1126/scitranslmed.aac5608. PMID:26606969.
  • Rossaint J, Kühne K, Skupski J, Aken HV, Looney MR, Hidalgo A, Zarbock A. Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat Commun. 2016;7:13464. doi:10.1038/ncomms13464. PMID:27845343.
  • Hezel ME, Nieuwland R, Bruggen RV, Juffermans NP. The ability of extracellular vesicles to induce a pro-inflammatory host response. Int J Mol Sci. 2017;18(6):1285. doi:10.3390/ijms18061285.
  • Kucharzik T, Walsh S, Chen J, Parkos C, Nusrat A. Neutrophil transmigration in inflammatory bowel disease is associated with altered expression of intercellular junction proteins. Gastroenterology. 2001;120(5):2001–9. doi:10.1016/s0016-5085(01)80927-6.
  • Koelink PJ, Overbeek SA, Braber S, Morgan ME, Henricks PA, Roda MA, Kraneveld AD. Collagen degradation and neutrophilic infiltration: a vicious circle in inflammatory bowel disease. Gut. 2013;63(4):578–87. doi:10.1136/gutjnl-2012-303252. PMID:23525573.
  • Michielan A, D'Incà R. Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of Leaky Gut. Mediat Inflamm. 2015;2015:628157. doi:10.1155/2015/628157.
  • Landy J, Ronde E, English N, Clark SK, Hart AL, Knight SC, Al-Hassi HO. Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. World J Gastroenterol. 2016;22(11):3117. doi:10.3748/wjg.v22.i11.3117. PMID:27003989.
  • Schlegel N, Meir M, Heupel WM, Holthofer B, Leube RE, Waschke J. Desmoglein 2-mediated adhesion is required for intestinal epithelial barrier integrity. AJP Gastrointest Liver Physiol. 2010;298(5):774–83. doi:10.1152/ajpgi.00239.2009.
  • Ungewiß H, Vielmuth F, Suzuki ST, Maiser A, Harz H, Leonhardt H, Waschke J. Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase. Sci Rep. 2017;7(1):6329. doi:10.1038/s41598-017-06713-y. PMID:28740231.
  • Lie PP, Cheng CY, Mruk DD. Crosstalk between desmoglein-2/desmocollin-2/Src kinase and coxsackie and adenovirus receptor/ZO-1 protein complexes, regulates blood-testis barrier dynamics. Int J Biochem Cell Biol. 2010;42(6):975–86. doi:10.1016/j.biocel.2010.02.010. PMID:20188849.
  • Symowicz J, Adley BP, Gleason KJ, Johnson JJ, Ghosh S, Fishman DA, Stack MS. Engagement of collagen-binding integrins promotes matrix metalloproteinase-9-dependent E-cadherin ectodomain shedding in Ovarian Carcinoma Cells. Cancer Res. 2007;67(5):2030–39. doi:10.1158/0008-5472.can-06-2808. PMID:17332331.
  • Gao H, Lan X, Li S, Xue Y. Relationships of MMP-9, E-cadherin, and VEGF expression with clinicopathological features and response to chemosensitivity in gastric cancer. Tumor Biol. 2017;39(5):1–7. doi:10.1177/1010428317698368.
  • Campbell HK, Maiers JL, Demali KA. Interplay between tight junctions & adherens junctions. Exp Cell Res. 2017;358(1):39–44. doi:10.1016/j.yexcr.2017.03.061. PMID:28372972.
  • Madrigal-Matute J, Lindholt JS, Fernandez-Garcia CE, Benito-Martin A, Burillo E, Zalba G, Martin-Ventura JL. Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis. J Am Heart Assoc. 2014;3(4):e000785. doi:10.1161/jaha.114.000785.
  • Jiang K, Rankin CR, Nava P, Sumagin R, Kamekura R, Stowell SR, Nusrat A. Galectin-3 Regulates Desmoglein-2 and intestinal epithelial intercellular adhesion. J Biol Chem. 2014;289(15):10510–7. doi:10.1074/jbc.m113.538538. PMID:24567334.
  • Eken C, Martin PJ, Sadallah S, Treves S, Schaller M, Schifferli JA. Ectosomes released by polymorphonuclear neutrophils induce a MerTK-dependent anti-inflammatory pathway in macrophages. J Biol Chem. 2010;285(51):39914–21. doi:10.1074/jbc.m110.126748. PMID:20959443.
  • Eken C, Sadallah S, Martin PJ, Treves S, Schifferli JA. Ectosomes of polymorphonuclear neutrophils activate multiple signaling pathways in macrophages. Immunobiology. 2013;218(3):382–92. doi:10.1016/j.imbio.2012.05.021. PMID:22749214.
  • Ma TY. TNF-α -induced increase in intestinal epithelial tight junction permeability requires NFκB activation. AJP Gastrointest Liver Physiol. 2004;286(3):367–76. doi:10.1152/ajpgi.00173.2003.
  • Al-Sadi R, Guo S, Ye D, Ma TY. TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1. Am J Pathol. 2013;183(6):1871–84. doi:10.1016/j.ajpath.2013.09.001. PMID:24121020.
  • Mazzon E, Cuzzocrea S. Role of TNF-α in ileum tight junction alteration in mouse model of restraint stress. AJP Gastrointest Liver Physiol. 2008;294(5):1268–80. doi:10.1152/ajpgi.00014.2008.
  • Cichon C, Sabharwal H, Rüter C, Schmidt MA. MicroRNAs regulate tight junction proteins and modulate epithelial/endothelial barrier functions. Tissue Barriers. 2014;2(4):e944446. doi:10.4161/21688362.2014.944446. PMID:25610754.
  • Zhou Q, Croce CM, Souba WW, Verne GN. Micro-RNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut. 2010;59(6):775–84. doi:10.1136/gut.2009.181834.
  • Zhou Q, Costinean S, Croce CM, Brasier AR, Merwat S, Larson SA, Verne GN. MicroRNA 29 targets nuclear factor-κB–repressing factor and Claudin 1 to increase intestinal permeability. Gastroenterology. 2015;148(1):158–169. doi:10.1053/j.gastro.2014.09.037.
  • Nolte-t H. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood. 2009;113(9):1977–81. (2009). doi:10.1182/blood-2009-08-237313. PMID:19064723.
  • Ludwig K, Fassan M, Mescoli C, Pizzi M, Balistreri M, Albertoni L, Rugge M. PDCD4/miR-21 dysregulation in inflammatory bowel disease-associated carcinogenesis. Virchows Arch. 2012;462(1):57–63. doi:10.1007/s00428-012-1345-5. PMID:23224068.
  • Wu F, Zikusoka M, Trindade A, Dassopoulos T, Harris ML, Bayless TM, Kwon JH. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2α. Gastroenterology. 2008;135(5):1624–35. doi:10.1053/j.gastro.2008.07.068.
  • Shi C, Liang Y, Yang J, Xia Y, Chen H, Han H, Qin H. MicroRNA-21 knockout improve the survival rate in DSS induced fatal colitis through protecting against inflammation and tissue injury. PLoS ONE. 2013;8(6):e66814. doi:10.1371/journal.pone.0066814.
  • Zhang L, Shen J, Cheng J, Fan X. MicroRNA-21 regulates intestinal epithelial tight junction permeability. Cell Biochem Funct. 2015;33(4):235–40. doi:10.1002/cbf.3109. PMID:25997617.
  • Ho B, Yu I, Lu L, Rudensky A, Chen H, Tsai C, Yu S. Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon. Nat Commun. 2014;5:3344. doi:10.1038/ncomms4344.
  • Mortazavi-Jahromi S, Jamshidi MM, Farazmand A, Aghazadeh Z, Yousefi M, Mirshafiey A. Pharmacological effects of β- d -mannuronic acid (M2000) on miR-146a, IRAK1, TRAF6 and NF-κB gene expression, as target molecules in inflammatory reactions. Pharmacol Rep. 2017;69(3):479–84. doi:10.1016/j.pharep.2017.01.021. PMID:28324845.
  • Alexander M, Hu R, Runtsch MC, Kagele DA, Mosbruger TL, Tolmachova T, O'Connell RM. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun. 2015;6:7321. doi:10.1038/ncomms8321. PMID:26084661.
  • Roos J, Enlund E, Funcke J, Tews D, Holzmann K, Debatin K, Fischer-Posovszky P. MiR-146a-mediated suppression of the inflammatory response in human adipocytes. Sci Rep. 2016;6(1):38339. doi:10.1038/srep38339.
  • He X, Zheng Y, Liu S, Shi S, Liu Y, He Y, Zhou X. MiR-146a protects small intestine against ischemia/reperfusion injury by down-regulating TLR4/TRAF6/NF-κB pathway. J Cell Physiol. 2017;233(3):2476–88. doi:10.1002/jcp.26124.
  • Luo X, Han M, Liu J, Wang Y, Luo X, Zheng J, Li H. Epithelial cell-derived micro RNA-146a generates interleukin-10-producing monocytes to inhibit nasal allergy. Sci Rep. 2015;5(1):15937. doi:10.1038/srep15937.
  • Zhou R, Ohara SP, Chen X. MicroRNA regulation of innate immune responses in epithelial cells. Cell Mol Immunol. 2011;8(5):371–9. doi:10.1038/cmi.2011.19. PMID:21725335.
  • Pigati L, Yaddanapudi SC, Iyengar R, Kim D, Hearn SA, Danforth D, Duelli DM. Selective release of MicroRNA species from normal and malignant mammary epithelial cells. PLoS ONE. 2010;5(10):e13515. doi:10.1371/journal.pone.0013515. PMID:20976003.
  • Awad W, Hess C, Hess M. Enteric pathogens and their toxin-induced disruption of the intestinal barrier through alteration of tight junctions in chickens. Toxins. 2017;9(2):60. doi:10.3390/toxins9020060.
  • Riddle MS, Porter CK. Detection bias and the association between inflammatory bowel disease and Salmonella and Campylobacter infection. Gut. 2011;61(4):635. doi:10.1136/gutjnl-2011-300617. PMID:21730102.
  • Hu G, Gong A, Roth AL, Huang BQ, Ward HD, Zhu G, Chen X. Release of luminal exosomes contributes to TLR4-mediated epithelial antimicrobial defense. PLoS Pathog. 2013;9(4):e1003261. doi:10.1371/journal.ppat.1003261.
  • Hill RH. Prevention of adhesion by indigenous bacteria to rabbit cecum epithelium by a barrier of microvesicles. Infect Immun. 1985;47(2):540–3. PMID:3881354.
  • Niel GV. Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice. Gut. 2003;52(12):1690–7. doi:10.1136/gut.52.12.1690. PMID:14633944.
  • Chen X, Song C, Feng B, Li T, Li P, Zheng P, Yang P. Intestinal epithelial cell-derived integrin 6 plays an important role in the induction of regulatory T cells and inhibits an antigen-specific Th2 response. J Leukoc Biol. 2011;90(4):751–9. doi:10.1189/jlb.1210696. PMID:21724807.
  • Evans-Osses I, Mojoli A, Monguió-Tortajada M, Marcilla A, Aran V, Amorim M, Ramirez MI. Microvesicles released from Giardia intestinalis disturb host-pathogen response in vitro. Eur J Cell Biol. 2017;96(2):131–42. doi:10.1016/j.ejcb.2017.01.005. PMID:28236495.
  • Slater TW, Finkielsztein A, Mascarenhas LA, Mehl LC, Butin-Israeli V, Sumagin R. Neutrophil microparticles deliver active myeloperoxidase to injured mucosa to inhibit epithelial wound healing. J Immunol. 2017;198(7):2886–97. doi:10.4049/jimmunol.1601810. PMID:28242649.
  • Pitanga T, França LD, Rocha VC, Meirelles T, Borges VM, Gonçalves M, Dos-Santos WL. Neutrophil-derived microparticles induce myeloperoxidase-mediated damage of vascular endothelial cells. BMC Cell Biol. 2014;15(1):21. doi:10.1186/1471-2121-15-21. PMID:24915973.
  • Hong Y, Eleftherio D, Hussain AA, Brogan PA. Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. J Am Soc Nephrol. 2012;23(1):49–62. doi:10.1681/ASN.2011030298. PMID:22052057.
  • Folkesson M, Li C, Frebelius S, Swedenborg J, Wågsäter D, Williams KJ, Liu M. Proteolytically active ADAM10 and ADAM17 carried on membrane microvesicles in human abdominal aortic aneurysms. Thromb Haemost. 2015;114(6):1165–1174. doi:10.1160/th14-10-0899. PMID:26422658.
  • Mesri M, Altieri DC. Leukocyte microparticles stimulate endothelial cell cytokine release and tissue factor induction in a JNK1 signaling pathway. J Biol Chem. 1999;274(33):23111–8. doi:10.1074/jbc.274.33.23111. PMID:10438480.
  • Vince RV, Chrismas B, Midgley AW, Mcnaughton LR, Madden LA. Hypoxia mediated release of endothelial microparticles and increased association of S100A12 with circulating neutrophils. Oxid Med Cell Longev. 2009;2(1):2–6. doi:10.4161/oxim.2.1.7611. PMID:20046638.
  • Wang Y, Tian J, Tang X, Rui K, Tian X, Ma J, Wang S. Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice. Oncotarget. 2016;7(13):15356–68. doi:10.18632/oncotarget.7324. PMID:26885611.
  • Véron P, Segura E, Sugano G, Amigorena S, Théry C. Accumulation of MFG-E8/lactadherin on exosomes from immature dendritic cells. Blood Cells Mol Dis. 2005;35(2):81–88. doi:10.1016/j.bcmd.2005.05.001. PMID:15982908.
  • Zhang Y, Brenner M, Yang W, Wang P. Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice. Lab Invest. 2015;95(5):480–90. doi:10.1038/labinvest.2015.32. PMID:25751740.
  • Scapini P, Cassatella MA. Social networking of human neutrophils within the immune system. Blood. 2014;124(5):710–9. doi:10.1182/blood-2014-03-453217. PMID:24923297.
  • Dalli J, Serhan CN. Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators. Blood. 2012;120(15):e60–72. doi:10.1182/blood-2012-04-423525. PMID:22904297.
  • Yang M, Chen J, Su F, Yu B, Su F, Lin L, Song E. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer. 2011;10(1):117. doi:10.1186/1476-4598-10-117. PMID:21939504.
  • Neudecker V, Haneklaus M, Jensen O, McNamee EN. Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome. J Exp Med. 2017;214(6):1737–52. doi:10.1084/jem.20160462. PMID:28487310.
  • Dalli J, Norling LV, Renshaw D, Cooper D, Leung K, Perretti M. Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles. Blood. 2008;112(6):2512–9. doi:10.1182/blood-2008-02-140533. PMID:18594025.
  • Borges FT, Melo SA, Ozdemir BC, Kato N, Revuelta I, Miller CA, Kalluri R. TGF- 1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J Am Soc Nephrol. 2012;24(3):385–92. doi:10.1681/asn.2012101031. PMID:23274427.
  • Pi B. Wound healing and the role of fibroblasts. J Wound Care. 2013;22(8):407–12. doi:10.12968/jowc.2013.22.8.407. PMID:23924840.
  • Luga V, Zhang L, Viloria-Petit A, Ogunjimi A, Inanlou M, Chiu E, Wrana J. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell. 2012;151(7):1542–56. doi:10.1016/j.cell.2012.11.024. PMID:23260141.
  • Pereira-Fantini PM, Judd LM, Kalantzis A, Peterson A, Ernst M, Heath JK, Giraud AS. A33 antigen-deficient mice have defective colonic mucosal repair. Inflamm Bowel Dis. 2010;16(4):604–12. doi:10.1002/ibd.21114. PMID:19856415.
  • Nomachi A, Nishita M, Inaba D, Enomoto M, Hamasaki M, Minami Y. Receptor Tyrosine Kinase Ror2 Mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal Kinase via actin-binding protein filamin A. J Biol Chem. 2008;283(41):27973–81. doi:10.1074/jbc.m802325200. PMID:18667433.
  • Miyoshi H. Wnt-expressing cells in the intestines: guides for tissue remodeling. J Biochem. 2016;161(1):19–25. doi:10.1093/jb/mvw070. PMID:28013225.
  • Harada T, Yamamoto H, Kishida S, Kishida M, Awada C, Takao T, Kikuchi A. Wnt5b-associated exosomes promote cancer cell migration and proliferation. Cancer Sci. 2016;108(1):42–52. doi:10.1111/cas.13109. PMID:27762090.
  • Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7(9):678–89. doi:10.1038/nri2156. PMID:17717539.
  • Sumagin R, Sarelius IH. Intercellular adhesion molecule-1 enrichment near tricellular endothelial junctions is preferentially associated with leukocyte transmigration and signals for reorganization of these junctions to accommodate leukocyte passage. J Immunol. 2010;184(9):5242–52. doi:10.4049/jimmunol.0903319. PMID:20363969.
  • Qian B, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Pollard JW. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011;475(7355):222–5. doi:10.1038/nature10138. PMID:21654748.
  • Tang N, Sun B, Gupta A, Rempel H, Pulliam L. Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-κB in endothelial cells. FASEB J. 2016;30(9):3097–106. doi:10.1096/fj.201600368rr. PMID:27226520.
  • Cerutti C, Soblechero-Martin P, Wu D, Lopez-Ramirez MA, Vries HD, Sharrack B, Romero IA. MicroRNA-155 contributes to shear-resistant leukocyte adhesion to human brain endothelium in vitro. Fluids Barriers CNS. 2016;13(1):8–15. doi:10.1186/s12987-016-0032-3. PMID:27246706.
  • Béres NJ, Szabó D, Kocsis D, Szűcs D, Kiss Z, Müller KE, Veres G. Role of altered expression of miR-146a, miR-155, and miR-122 in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22(2):327–35. doi:10.1097/mib.0000000000000687. PMID:26752469.
  • Fasseu M, Tréton X, Guichard C, Pedruzzi E, Cazals-Hatem D, Richard C, Ogier-Denis E. Identification of Restricted Subsets of Mature microRNA abnormally expressed in inactive colonic mucosa of patients with inflammatory bowel disease. PLoS ONE. 2010;5(10):e13160. doi:10.1371/journal.pone.0013160.
  • Yoshimura A, Suzuki M, Sakaguchi R, Yasukawa H. SOCS, inflammation, and autoimmunity. Front Immunol. 2012;3:20. doi:10.3389/fimmu.2012.00020. PMID:22566904.
  • Pathak S, Grillo AR, Scarpa M, Brun P, Dincà R, Nai L, Castagliuolo I. MiR-155 modulates the inflammatory phenotype of intestinal myofibroblasts by targeting SOCS1 in ulcerative colitis. Exp Mol Med. 2015;47(5):e164. doi:10.1038/emm.2015.21. PMID:25998827.
  • Wong W, Lee MM, Chan BD, Kam RK, Zhang G, Lu A, Tai WC. Proteomic profiling of dextran sulfate sodium induced acute ulcerative colitis mice serum exosomes and their immunomodulatory impact on macrophages. Proteomics. 2016;16(7):1131–45. doi:10.1002/pmic.201500174. PMID:26806198.
  • Shinichiro H, Masaru H, Hironori K, Takumi K, Eitaro T, Ryukichi K, Michio S. Tumor necrosis factor-alpha and interferon-gamma directly impair epithelial barrier function in cultured mouse cholangiocytes. Liver Int. 2003;23(1):3–11. doi:10.1034/j.1600-0676.2003.01707.x.
  • Kaiser G, Polk D. Tumor necrosis factor alpha regulates proliferation in a mouse intestinal cell line. Gastroenterology. 1997;112(4):1231–40. doi:10.1016/s0016-5085(97)70135-5. PMID:9098007.
  • Schmitz H, Fromm M, Bentzel CJ, Schulzke JD. Tumor necrosis factor α (TNFα) impairs barrier function in epithelial monolayers of HT-29/B6 cells. Gastroenterology. 1999;108(4):137–46. doi:10.1016/0016-5085(95)23946-4.
  • Williams MR, Luscinskas FW. Leukocyte rolling and adhesion via ICAM-1 signals to endothelial permeability. Focus on “Leukocyte rolling and adhesion both contribute to regulation of microvascular permeability to albumin via ligation of ICAM-1”. AJP Cell Physiol. 2011;301(4):777–9. doi:10.1152/ajpcell.00250.2011.
  • Zhao C, Sardella A, Chun J, Poubelle PE, Fernandes MJ, Bourgoin SG. TNF-α promotes LPA1- and LPA3-mediated recruitment of leukocytes in vivo through CXCR2 ligand chemokines. J Lipid Res. 2011;52(7):1307–18. doi:10.1194/jlr.m008045. PMID:21521824.
  • Kojima M, Gimenes-Junior JA, Chan TW, Eliceiri BP, Baird A, Costantini TW, Coimbra R. Exosomes in postshock mesenteric lymph are key mediators of acute lung injury triggering the macrophage activation via Toll-like receptor 4. FASEB J. 2017;32(1):97–110. doi:10.1096/fj.201700488r.
  • Lee HM, Choi E, Kim JH, Kim TD, Kim Y, Kang C, Gho YS. A membranous form of ICAM-1 on exosomes efficiently blocks leukocyte adhesion to activated endothelial cells. Biochem Biophys Res Commun. 2010;397(2):251–6. doi:10.1016/j.bbrc.2010.05.094. PMID:20529672.
  • Nakamura Y, Miyaki S, Ishitobi H, Matsuyama S, Nakasa T, Kamei N, Ochi M. Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration. FEBS Lett. 2015;589(11):1257–65. doi:10.1016/j.febslet.2015.03.031. PMID:25862500.
  • Lin J, Welker NC, Zhao Z, Li Y, Zhang J, Reuss SA, Bronner MP. Novel specific microRNA biomarkers in idiopathic inflammatory bowel disease unrelated to disease activity. Mod Pathol. 2013;27(4):602–8. doi:10.1038/modpathol.2013.152. PMID:24051693.
  • Keklikoglou I, Hosaka K, Bender C, Bott A, Koerner C, Mitra D, Wiemann S. MicroRNA-206 functions as a pleiotropic modulator of cell proliferation, invasion and lymphangiogenesis in pancreatic adenocarcinoma by targeting ANXA2 and KRAS genes. Oncogene. 2014;34(37):4867–78. doi:10.1038/onc.2014.408. PMID:25500542.
  • Hao X, Li Z, Ma Y, Wang J, Zeng X, Li R, Kang W. Exosomal microRNA-141 is upregulated in the serum of prostate cancer patients. Onco Targets Ther. 2015;9:139–148. doi:10.2147/ott.s95565.
  • Huang Z, Shi T, Zhou Q, Shi S, Zhao R, Shi H, Zhang J. MiR-141 Regulates colonic leukocytic trafficking by targeting CXCL12β during murine colitis and human Crohns disease. Gut. 2013;63(8):1247–57. doi:10.1136/gutjnl-2012-304213. PMID:24000293.
  • Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA. Rapid Changes in MicroRNA-146a expression negatively regulate the IL-1-induced inflammatory response in human lung alveolar epithelial cells. J Immunol. 2008;180(8):5689–98. doi:10.4049/jimmunol.180.8.5689. PMID:18390754.
  • Lee H, Zhang D, Zhu Z, Cruz CS, Jin Y. Epithelial cell-derived microvesicles activate macrophages and promote inflammation via microvesicle-containing microRNAs. Sci Rep. 2016;6(1):35250. doi:10.1038/srep35250.
  • Esser J, Gehrmann U, Dalexandri FL, Hidalgo-Estévez AM, Wheelock CE, Scheynius A, Rådmark O. Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration. J Allergy Clin Immunol. 2010;126(5):1032–40. doi:10.1016/j.jaci.2010.06.039. PMID:20728205.
  • Harada A, Sekido N, Akahoshi T, Wada T, Mukaida N, Matsushima K. Establishment of essential involvement of IL-8 in acute inflammation. Cytokine. 1994;6(5):547. doi:10.1016/1043-4666(94)90129-5.
  • Leung BP, Culshaw S, Gracie JA, Hunter D, Canetti CA, Campbell C, Mcinnes IB. A Role for IL-18 in neutrophil activation. J Immunol. 2001;167(5):2879–86. doi:10.4049/jimmunol.167.5.2879. PMID:11509635.
  • Subra C, Grand D, Laulagnier K, Stella A, Lambeau G, Paillasse M, Record M. Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J Lipid Res. 2010;51(8):2105–20. doi:10.1194/jlr.m003657. PMID:20424270.
  • Scandella E. Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood. 2002;100(4):1354–61. doi:10.1182/blood-2001-11-0017. PMID:12149218.
  • Ha D, Yang N, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm Sin B. 2016;6(4):287–96. doi:10.1016/j.aps.2016.02.001. PMID:27471669.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.