Biogenesis and function of T cell-derived exosomes

Frontiers in Cell and Developmental Biology

Volumn 4, Issue AUG, 2016, Pages

  Ventimiglia, Leandro N ^a,b   Alonso, Miguel A ^a  

^a UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^b KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Condensed membranes; ESCRT complex; Exosomes; MAL protein; Multivesicular endosomes; Tetraspanins

Indexed keywords

EID: 85018494258     PISSN: None     EISSN: 2296634X     Source Type: Journal    
DOI: 10.3389/fcell.2016.00084     Document Type: Short Survey

References (108)

1. Admyre, C., Grunewald, J., Thyberg, J., Gripenbäck, S., Tornling, G., Eklund, A., et al. (2003). Exosomes with major histocompatibility complex class II and co-stimulatory molecules are present in human BAL fluid. Eur. Respir. J. 22, 578-583. doi: 10.1183/09031936.03.00041703
2. Admyre, C., Johansson, S. M., Qazi, K. R., Filén, J. J., Lahesmaa, R., Norman, M., et al. (2007). Exosomes with immune modulatory features are present in human breast milk. J. Immunol. 179, 1969-1978. doi: 10.4049/jimmunol.179.3.1969
3. Agarwal, A., Fanelli, G., Letizia, M., Tung, S. L., Boardman, D., Lechler, R., et al. (2014). Regulatory T cell-derived exosomes: possible therapeutic and diagnostic tools in transplantation. Front. Immunol. 5:555. doi: 10.3389/fimmu.2014.00555
4. Alonso, M. A., and Weissman, S. M. (1987). cDNA cloning and sequence of MAL, a hydrophobic protein associated with human T-cell differentiation. Proc. Natl. Acad. Sci. U.S.A. 84, 1997-2001. doi: 10.1073/pnas.84.7.1997
5. Alonso, R., Mazzeo, C., Rodríguez, M. C., Marsh, M., Fraile-Ramos, A., Calvo, V., et al. (2011). Diacylglycerol kinase a regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes. Cell Death Differ. 18, 1161-1173. doi: 10.1038/cdd.2010.184
6. Alonso, R., Rodríguez, M. C., Pindadolh, J., Merino, E., Mérida, I., and Izquierdo, M. (2005). Diacylglycerol kinase alpha regulates the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes. J. Biol. Chem. 280, 28439-28450. doi: 10.1074/jbc.M501112200
7. Andre, F., Schartz, N. E. C., Movassagh, M., Flament, C., Pautier, P., Morice, P., et al. (2002). Malignant effusions and immunogenic tumour-derived exosomes. Lancet 360, 295-305. doi: 10.1016/S0140-6736(02)09552-1
8. Andreu, Z., and Yáñez-Mó, M. (2014). Tetraspanins in extracellular vesicle formation and function. Front. Immunol. 5:442. doi: 10.3389/fimmu.2014.00442
9. Antón, O., Batista, A., Millán, J., Andrés-Delgado, L., Puertollano, R., Correas, I., et al. (2008). An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes. J. Exp. Med. 205, 3201-3213. doi: 10.1084/jem.20080552
10. Antón, O. M., Andrés-Delgado, L., Reglero-Real, N., Batista, A., and Alonso, M. A. (2011). MAL protein controls protein sorting at the supramolecular activation cluster of human T lymphocytes. J. Immunol. 186, 6345-6356. doi: 10.4049/jimmunol.1003771
11. Arenaccio, C., Chiozzini, C., Columba-Cabezas, S., Manfredi, F., Affabris, E., Baur, A., et al. (2014a). Exosomes from human immunodeficiency virus type 1 (HIV-1)-infected cells license quiescent CD4+ T lymphocytes to replicate HIV-1 through a Nef-and ADAM17-dependent mechanism. J. Virol. 88, 11529-11539. doi: 10.1128/JVI.01712-14
12. Arenaccio, C., Chiozzini, C., Columba-Cabezas, S., Manfredi, F., and Federico, M. (2014b). Cell activation and HIV-1 replication in unstimulated CD4+ T lymphocytes ingesting exosomes from cells expressing defective HIV-1. Retrovirology 11:46. doi: 10.1186/1742-4690-11-46
13. Babst, M., Katzmann, D. J., Estepa-Sabal, E. J., Meerloo, T., and Emr, S. D. (2002a). ESCRT-III: an endosome-associated heterooligomeric protein complex required for MVB sorting. Dev. Cell 3, 271-282. doi: 10.1016/S1534-5807(02)00220-4
14. Babst, M., Katzmann, D. J., Snyder, W. B., Wendland, B., and Emr, S. D. (2002b). Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body. Dev. Cell 3, 283-289. doi: 10.1016/S1534-5807(02)00219-8
15. Bache, K. G., Brech, A., Mehlum, A., and Stenmark, H. (2003). Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes. J. Cell Biol. 162, 435-442. doi: 10.1083/jcb.200302131
16. Baietti, M. F., Zhang, Z., Mortier, E., Melchior, A., Degeest, G., Geeraerts, A., et al. (2012). Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 14, 677-685. doi: 10.1038/ncb2502
17. Bissig, C., and Gruenberg, J. (2013). Lipid sorting and multivesicular endosome biogenesis. Cold Spring Harb. Perspect. Biol. 5:a016816. doi: 10.1101/cshperspect.a016816
18. Bissig, C., and Gruenberg, J. (2014). ALIX and the multivesicular endosome: ALIX in Wonderland. Trends Cell Biol. 24, 19-25. doi: 10.1016/j.tcb.2013.10.009
19. Blanchard, N., Lankar, D., Faure, F., Regnault, A., Dumont, C., Raposo, G., et al. (2002). TCR Activation of human T cells induces the production of exosomes bearing the TCR/CD3 complex. J. Immunol. 168, 3235-3241. doi: 10.4049/jimmunol.168.7.3235
20. Bosque, A., Dietz, L., Gallego-Lleyda, A., Sanclemente, M., Iturralde, M., Naval, J., et al. (2016). Comparative proteomics of exosomes secreted by tumoral Jurkat T cells and normal human T cell blasts unravels a potential tumorigenic role for valosin-containing protein. Oncotarget. doi: 10.18632/oncotarget.8678. [Epub ahead of print]
21. Bryniarski, K., Ptak, W., Jayakumar, A., Püllmann, K., Caplan, M. J., Chairoungdua, A., et al. (2013). Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity. J. Allergy Clin. Immunol. 132, 170-181. doi: 10.1016/j.jaci.2013.04.048
22. Buschow, S. I., Nolte-'t Hoen, E. N. M., van Niel, G., Pols, M. S., ten Broeke, T., Lauwen, M., et al. (2009). MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic 10, 1528-1542. doi: 10.1111/j.1600-0854.2009.00963.x
23. Caby, M.-P., Lankar, D., Vincendeau-Scherrer, C., Raposo, G., and Bonnerot, C. (2005). Exosomal-like vesicles are present in human blood plasma. Int. Immunol. 17, 879-887. doi: 10.1093/intimm/dxh267
24. Cai, Z., Yang, F., Yu, L., Yu, Z., Jiang, L., Wang, Q., et al. (2012). Activated T cell exosomes promote tumor invasion via Fas signaling pathway. J. Immunol. 188, 5954-5961. doi: 10.4049/jimmunol.1103466
25. Campbell, T. D., Khan, M., Huang, M., Bond, V. C., and Powell, M. D. (2008). HIV-1 Nef protein is secreted into vesicles that can fuse with target cells and virions. Ethn. Dis. 18(2 Suppl. 2):S2-14-9
26. Castro, B. M., Prieto, M., and Silva, L. C. (2014). Ceramide: a simple sphingolipid with unique biophysical properties. Prog. Lipid Res. 54, 53-67. doi: 10.1016/j.plipres.2014.01.004
27. Chairoungdua, A., Smith, D. L., Pochard, P., Hull, M., and Caplan, M. J. (2010). Exosome release of β-catenin: a novel mechanism that antagonizes Wnt signaling. J. Cell Biol. 190, 1079-1091. doi: 10.1083/jcb.201002049
28. Chang, W. J., Rothberg, K. G., Kamen, B. A., and Anderson, R. G. W. (1992). Lowering the cholesterol content of MA104 cells inhibits receptor-mediated transport of folate. J. Cell Biol. 118, 63-69. doi: 10.1083/jcb.118.1.63
29. Charrin, S., Jouannet, S., Boucheix, C., and Rubinstein, E. (2014). Tetraspanins at a glance. J. Cell Sci. 127, 3641-3648. doi: 10.1242/jcs.154906
30. Cherukuri, A., Shoham, T., Sohn, H. W., Levy, S., Brooks, S., Carter, R., et al. (2004). The tetraspanin CD81 is necessary for partitioning of coligated CD19/CD21-B cell antigen receptor complexes into signaling-active lipid rafts. J. Immunol. 172, 370-380. doi: 10.4049/jimmunol.172.1.370
31. Choi, D.-S., Kim, D.-K., Kim, Y.-K., and Gho, Y. S. (2015). Proteomics of extracellular vesicles: exosomes and ectosomes. Mass Spectrom. Rev. 34, 474-490. doi: 10.1002/mas.21420
32. Colombo, M., Moita, C., van Niel, G., Kowal, J., Vigneron, J., Benaroch, P., et al. (2013). Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 126, 5553-5565. doi: 10.1242/jcs.128868
33. De Gassart, A., Géminard, C., Février, B., Raposo, G., and Vidal, M. (2003). Lipid raft-associated protein sorting in exosomes. Blood 102, 4336-4344. doi: 10.1182/blood-2003-03-0871
34. Delaguillaumie, A., Harriague, J., Kohanna, S., Bismuth, G., Rubinstein, E., Seigneuret, M., et al. (2004). Tetraspanin CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes: relevance to co-stimulation. J. Cell Sci. 117, 5269-5282. doi: 10.1242/jcs.01380
35. De Toro, J., Herschlik, L., Waldner, C., and Mongini, C. (2015). Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Front. Immunol. 6:203. doi: 10.3389/fimmu.2015.00203
36. Dubois, L., Ronquist, K., Ek, B., Ronquist, G., and Larsson, A. (2015). Proteomic profiling of detergent resistant membranes (lipid rafts) of prostasomes. Mol. Cell. Proteomics 14, 3015-3022. doi: 10.1074/mcp.M114.047530
37. Escola, J. M., Kleijmeer, M. J., Stoorvogel, W., Griffith, J. M., Yoshie, O., and Geuze, H. J. (1998). Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J. Biol. Chem. 273, 20121-20127. doi: 10.1074/jbc.273.32.20121
38. Géminard, C., de Gassart, A., Blanc, L., and Vidal, M. (2004). Degradation of AP2 during reticulocyte maturation enhances binding of hsc70 and Alix to a common site on TfR for sorting in exosomes. Traffic 5, 181-193. doi: 10.1111/j.1600-0854.2004.0167.x
39. Hanson, P. I., and Cashikar, A. (2012). Multivesicular body morphogenesis. Annu. Rev. Cell Dev. Biol. 28, 337-362. doi: 10.1146/annurev-cellbio-092910-154152
40. Harding, C., Heuser, J., and Stahl, P. (1983). Receptor-mediated endocytosis of transferrin and of the transferrin receptor in rat reticulocytes. J. Cell Biol. 200, 367-371. doi: 10.1083/jcb.201212113
41. Heijnen, H. F. G., Schiel, A. E., Fijnheer, R., Geuze, H. J., and Sixma, J. J. (1999). Activated platelets release two types of membrane vesicles. Blood 94, 3791-3800
42. Heijnen, H. F. G., Van Lier, M., Waaijenborg, S., Ohno-Iwashita, Y., Waheed, A. A., Inomata, M., et al. (2003). Concentration of rafts in platelet filopodia correlates with recruitment of c-Src and CD63 to these domains. J. Thromb. Haemost. 1, 1161-1173. doi: 10.1046/j.1538-7836.2003.00316.x
43. Henne, W. M., Buchkovich, N. J., and Emr, S. D. (2011). The ESCRT pathway. Dev. Cell 21, 77-91. doi: 10.1016/j.devcel.2011.05.015
44. Huotari, J., and Helenius, A. (2011). Endosome maturation. EMBO J. 30, 3481-3500. doi: 10.1038/emboj.2011.286
45. Ishii, M., Iwai, K., Koike, M., Ohshima, S., Kudo-Tanaka, E., Ishii, T., et al. (2006). RANKL-induced expression of tetraspanin CD9 in lipid raft membrane microdomain is essential for cell fusion during osteoclastogenesis. J. Bone Miner. Res. 21, 965-976. doi: 10.1359/jbmr.060308
46. Johnstone, R. M., Adam, M., Hammond, J. R., Orr, L., and Turbide, C. (1987). Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 262, 9412-9420
47. Kalra, H., Simpson, R. J., Ji, H., Aikawa, E., Altevogt, P., Askenase, P., et al. (2012). Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 10:e1001450. doi: 10.1371/journal.pbio.1001450
48. Keller, S., Rupp, C., Stoeck, A., Runz, S., Fogel, M., Lugert, S., et al. (2007). CD24 is a marker of exosomes secreted into urine and amniotic fluid. Kidney Int. 72, 1095-1102. doi: 10.1038/sj.ki.5002486
49. Kobayashi, T., Stang, E., Fang, K. S., de Moerloose, P., Parton, R. G., and Gruenberg, J. (1998). A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 392, 193-197. doi: 10.1038/32440
50. Kosaka, N., Iguchi, H., Yoshioka, Y., Takeshita, F., Matsuki, Y., and Ochiya, T. (2010). Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 285, 17442-17452. doi: 10.1074/jbc.M110.107821
51. Laulagnier, K., Grand, D., Dujardin, A., Hamdi, S., Vincent-Schneider, H., Lankar, D., et al. (2004). PLD2 is enriched on exosomes and its activity is correlated to the release of exosomes. FEBS Lett. 572, 11-14. doi: 10.1016/j.febslet.2004.06.082
52. Lee, J. H., Wittki, S., Bräu, T., Dreyer, F. S., Krätzel, K., Dindorf, J., et al. (2013). HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases. Mol. Cell 49, 668-679. doi: 10.1016/j.molcel.2012.12.004
53. Le Naour, F., André, M., Boucheix, C., and Rubinstein, E. (2006). Membrane microdomains and proteomics: lessons from tetraspanin microdomains and comparison with lipid rafts. Proteomics 6, 6447-6454. doi: 10.1002/pmic.200600282
54. Lenassi, M., Cagney, G., Liao, M., Vaupotic, T., Bartholomeeusen, K., Cheng, Y., et al. (2010). HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells. Traffic 11, 110-122. doi: 10.1111/j.1600-0854.2009.01006.x
55. Lingwood, D., and Simons, K. (2010). Lipid rafts as a membrane-organizing principle. Science 327, 46-50. doi: 10.1126/science.1174621
56. Liu, Y., Gu, Y., and Caoa, X. (2015). The exosomes in tumor immunity. Oncoimmunology 4:e1027472. doi: 10.1080/2162402X.2015.1027472
57. Llorente, A., de Marco, M. C., and Alonso, M. A. (2004). Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line. J. Cell Sci. 117, 5343-5351. doi: 10.1242/jcs.01420
58. Llorente, A., Skotland, T., Sylvänne, T., Kauhanen, D., Róg, T., Orlowski, A., et al. (2013). Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim. Biophys. Acta 1831, 1302-1309. doi: 10.1016/j.bbalip.2013.04.011
59. Lugini, L., Cecchetti, S., Huber, V., Luciani, F., Macchia, G., Spadaro, F., et al. (2012). Immune surveillance properties of human NK cell-derived exosomes. J. Immunol. 189, 2833-2842. doi: 10.4049/jimmunol.1101988
60. Magal, L. G., Yaffe, Y., Shepshelovich, J., Aranda, J. F., de Marco, M. C., Gaus, K., et al. (2009). Clustering and lateral concentration of raft lipids by the MAL protein. Mol. Biol. Cell 20, 3751-3376. doi: 10.1091/mbc.E09-02-0142
61. Marks, M. S., Heijnen, H. F. G., and Raposo, G. (2013). Lysosome-related organelles: unusual compartments become mainstream. Curr. Opin. Cell Biol. 25, 495-505. doi: 10.1016/j.ceb.2013.04.008
62. Masyuk, A. I., Huang, B. Q., Ward, C. J., Gradilone, S. A., Banales, J. M., Masyuk, T. V., et al. (2010). Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G990-G999. doi: 10.1152/ajpgi.00093.2010
63. Matsuo, H., Chevallier, J., Mayran, N., Le Blanc, I., Ferguson, C., Faure, J., et al. (2004). Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science 531, 1-4. doi: 10.1126/science.1092425
64. Maxfield, F. R., and van Meer, G. (2010). Cholesterol, the central lipid of mammalian cells. Curr. Opin. Cell Biol. 22, 422-429. doi: 10.1016/j.ceb.2010.05.004
65. Mazurov, D., Barbashova, L., and Filatov, A. (2013). Tetraspanin protein CD9 interacts with metalloprotease CD10 and enhances its release via exosomes. FEBS J. 280, 1200-1213. doi: 10.1111/febs.12110
66. Millán, J., and Alonso, M. A. (1998). MAL, a novel integral membrane protein of human T lymphocytes, associates with glycosylphosphatidylinositol-anchored proteins and Src-like tyrosine kinases. Eur. J. Immunol. 28, 3675-3684
67. Mittelbrunn, M., Gutiérrez-Vázquez, C., Villarroya-Beltri, C., González, S., Sánchez-Cabo, F., González, M. á., et al. (2011). Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2, 282. doi: 10.1038/ncomms1285
68. Möbius, W., van Donselaar, E., Ohno-Iwashita, Y., Shimada, Y., Heijnen, H. F. G., Slot, J. W., et al. (2003). Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway. Traffic 4, 222-231. doi: 10.1034/j.1600-0854.2003.00072.x
69. Muratori, C., Cavallin, L. E., Kratzel, K., Tinari, A., De Milito, A., Fais, S., et al. (2009). Massive secretion by T cells is caused by HIV Nef in infected cells and by Nef transfer to bystander cells. Cell Host Microbe 6, 218-230. doi: 10.1016/j.chom.2009.06.009
70. Navabi, H., Croston, D., Hobot, J., Clayton, A., Zitvogel, L., Jasani, B., et al. (2005). Preparation of human ovarian cancer ascites-derived exosomes for a clinical trial. Blood Cells Mol. Dis. 35, 149-152. doi: 10.1016/j.bcmd.2005.06.008
71. Nguyen, D. G., Booth, A., Gould, S. J., and Hildreth, J. E. K. (2003). Evidence that HIV budding in primary macrophages occurs through the exosome release pathway. J. Biol. Chem. 278, 52347-52354. doi: 10.1074/jbc.M309009200
72. Ogawa, Y., Kanai-Azuma, M., Akimoto, Y., Kawakami, H., and Yanoshita, R. (2008). Exosome-like vesicles with dipeptidyl peptidase IV in human saliva. Biol. Pharm. Bull. 31, 1059-1062. doi: 10.1248/bpb.31.1059
73. Okoye, I. S., Coomes, S. M., Pelly, V. S., Czieso, S., Papayannopoulos, V., Tolmachova, T., et al. (2014). MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells. Immunity 41, 89-103. doi: 10.1016/j.immuni.2014.05.019
74. Pan, B. T., and Johnstone, R. M. (1983). The fate of the transferrin receptor during maturation of sheep reticulocytes in vitro. Cell 33, 967-977. doi: 10.1016/0092-8674(83)90040-5
75. Perez-Hernandez, D., Gutiérrez-Vázquez, C., Jorge, I., López-Martín, S., Ursa, A., Sánchez-Madrid, F., et al. (2013). The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. J. Biol. Chem. 288, 11649-11661. doi: 10.1074/jbc.M112.445304
76. Pisitkun, T., Shen, R.-F., and Knepper, M. A. (2004). Identification and proteomic profiling of exosomes in human urine. Proc. Natl. Acad. Sci. U.S.A. 101, 13368-13373. doi: 10.1073/pnas.0403453101
77. Poliakov, A., Spilman, M., Dokland, T., Amling, C. L., and Mobley, J. A. (2009). Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen. Prostate 69, 159-167. doi: 10.1002/pros.20860
78. Rabesandratana, H., Toutant, J. P., Reggio, H., and Vidal, M. (1998). Decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59) are released within exosomes during In vitro maturation of reticulocytes. Blood 91, 2573-2580
79. Raposo, G., Nijman, H. W., Stoorvogel, W., Liejendekker, R., Harding, C. V., Melief, C. J., et al. (1996). B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183, 1161-1172. doi: 10.1084/jem.183.3.1161
80. Raposo, G., and Stoorvogel, W. (2013). Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 200, 373-383. doi: 10.1083/jcb.201211138
81. Raymond, A. D., Campbell-Sims, T. C., Khan, M., Lang, M., Huang, M. B., Bond, V. C., et al. (2011). HIV Type 1 Nef is released from infected cells in CD45(+) microvesicles and is present in the plasma of HIV-infected individuals. AIDS Res. Hum. Retroviruses 27, 167-178. doi: 10.1089/aid.2009.0170
82. Rialland, P., Lankar, D., Raposo, G., Bonnerot, C., and Hubert, P. (2006). BCR-bound antigen is targeted to exosomes in human follicular lymphoma B-cells. Biol. Cell 98, 491-501. doi: 10.1042/BC20060027
83. Rooney, I. A., Atkinson, J. P., Krul, E. S., Schonfeld, G., Polakoski, K., Saffitz, J. E., et al. (1993). Physiologic relevance of the membrane attack complex inhibitory protein CD59 in human seminal plasma: CD59 is present on extracellular organelles (prostasomes), binds cell membranes, and inhibits complement-mediated lysis. J. Exp. Med. 177, 1409-1420. doi: 10.1084/jem.177.5.1409
84. Sáenz-Cuesta, M., Mittelbrunn, M., and Otaegui, D. (2015). Novel clinical applications of extracellular vesicles. Front. Immunol. 6:381. doi: 10.3389/fimmu.2015.00381
85. Schuh, A. L., and Audhya, A. (2014). The ESCRT machinery: from the plasma membrane to endosomes and back again. Crit. Rev. Biochem. Mol. Biol. 49, 242-261. doi: 10.3109/10409238.2014.881777
86. Shelton, M. N., Huang, M.-B., Ali, S. A., Powell, M. D., and Bond, V. C. (2012). Secretion modification region-derived peptide disrupts HIV-1 Nef's interaction with mortalin and blocks virus and Nef exosome release. J. Virol. 86, 406-419. doi: 10.1128/JVI.05720-11
87. Skokos, D., Le Panse, S., Villa, I., Rousselle, J.-C., Peronet, R., David, B., et al. (2001). Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes. J. Immunol. 166, 868-876. doi: 10.4049/jimmunol.166.2.868
88. Skriner, K., Adolph, K., Jungblut, P. R., and Burmester, G. R. (2006). Association of citrullinated proteins with synovial exosomes. Arthritis Rheum. 54, 3809-3814. doi: 10.1002/art.22276
89. Staubach, S., Razawi, H., and Hanisch, F. G. (2009). Proteomics of MUC1-containing lipid rafts from plasma membranes and exosomes of human breast carcinoma cells MCF-7. Proteomics 9, 2820-2835. doi: 10.1002/pmic.200800793
90. Subra, C., Laulagnier, K., Perret, B., and Record, M. (2007). Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89, 205-212. doi: 10.1016/j.biochi.2006.10.014
91. Tamai, K., Tanaka, N., Nakano, T., Kakazu, E., Kondo, Y., Inoue, J., et al. (2010). Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem. Biophys. Res. Commun. 399, 384-390. doi: 10.1016/j.bbrc.2010.07.083
92. Theos, A. C., Truschel, S. T., Tenza, D., Hurbain, I., Harper, D. C., Berson, J. F., et al. (2006). A lumenal domain-dependent pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis. Dev. Cell 10, 343-354. doi: 10.1016/j.devcel.2006.01.012
93. Thiele, C., Hannah, M. J., Fahrenholz, F., and Huttner, W. B. (2000). Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles. Nat. Cell Biol. 2, 42-49. doi: 10.1038/71366
94. Tkach, M., and Théry, C. (2016). Communication by extracellular vesicles: where we are and where to go. Cell 164, 1226-1232. doi: 10.1016/j.cell.2016.01.043
95. Trajkovic, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., et al. (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319, 1244-1247. doi: 10.1126/science.1153124
96. Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J., and Jan, L. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654-659. doi: 10.1038/ncb1596
97. van Niel, G., Charrin, S., Simoes, S., Romao, M., Rochin, L., Saftig, P., et al. (2011). The tetraspanin CD63 regulates ESCRT-independent and-dependent endosomal sorting during melanogenesis. Dev. Cell 21, 708-721. doi: 10.1016/j.devcel.2011.08.019
98. Vella, L. J., Greenwood, D. L. V., Cappai, R., Scheerlinck, J. P. Y., and Hill, A. F. (2008). Enrichment of prion protein in exosomes derived from ovine cerebral spinal fluid. Vet. Immunol. Immunopathol. 124, 385-393. doi: 10.1016/j.vetimm.2008.04.002
99. Ventimiglia, L. N., Fernández-Martín, L., Martínez-Alonso, E., Antón, O. M., Guerra, M., Martínez-Menárguez, J. A., et al. (2015). Regulation of exosome secretion by the integral MAL protein in T cells. J. Immunol. 195, 810-814. doi: 10.4049/jimmunol.1500891
100. Verweij, F. J., van Eijndhoven, M. A. J., Hopmans, E. S., Vendrig, T., Wurdinger, T., Cahir-McFarland, E., et al. (2011). LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activation. EMBO J. 30, 2115-2129. doi: 10.1038/emboj.2011.123
101. Wahlgren, J., Karlson, T. D. L., Glader, P., Telemo, E., and Valadi, H. (2012). Activated human T cells secrete exosomes that participate in IL-2-mediated immune response signaling. PLoS ONE 7:e49723. doi: 10.1371/journal.pone.0049723
102. Wu, G., Yang, G., Zhang, R., Xu, G., Zhang, L., Wen, W., et al. (2015). Altered microRNA expression profiles of extracellular vesicles in nasal mucus from patients with allergic rhinitis. Allergy Asthma Immunol. Res. 7, 449-457. doi: 10.4168/aair.2015.7.5.449
103. Wubbolts, R., Leckie, R. S., Veenhuizen, P. T. M., Schwarzmann, G., Möbius, W., Hoernschemeyer, J., et al. (2003). Proteomic and biochemical analyses of human B cell-derived exosomes: potential implications for their function and multivesicular body formation. J. Biol. Chem. 278, 10963-10972. doi: 10.1074/jbc.M207550200
104. Yáñez,-Mó, M., Barreiro, O., Gordon-Alonso, M., Sala-Valdés, M., and Sánchez-Madrid, F. (2009). Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol. 19, 434-446. doi: 10.1016/j.tcb.2009.06.004
105. Yu, X., Huang, C., Song, B., Xiao, Y., Fang, M., Feng, J., et al. (2013). CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model. Cell. Immunol. 285, 62-68. doi: 10.1016/j.cellimm.2013.06.010
106. Zhang, B., Yin, Y., Lai, R. C., and Lim, S. K. (2014). Immunotherapeutic potential of extracellular vesicles. Front. Immunol. 5:518. doi: 10.3389/fimmu.2014.00518
107. Zhang, H., Xie, Y., Li, W., Chibbar, R., Xiong, S., and Xiang, J. (2011). CD4(+) T cell-released exosomes inhibit CD8(+) cytotoxic T-lymphocyte responses and antitumor immunity. Cell. Mol. Immunol. 8, 23-30. doi: 10.1038/cmi.2010.59
108. Zitvogel, L., Regnault, A., Lozier, A., Wolfers, J., Flament, C., Tenza, D., et al. (1998). Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat. Med. 4, 594-600. doi: 10.1038/nm0598-594