Archivos suplementarios
Palabras clave
Exosoma
Inmunomodulación
Inmunoterapia
Biomarcador
Resumen
Las células liberan biomoléculas de diversa naturaleza a su entorno para comunicarse con las células vecinas. Además de dichas moléculas, secretan también elementos más complejos como las vesículas; estructuras compuestas por bicapas lipídicas con proteínas transmembranales que encierran un contenido hidrofílico. Los exosomas son un subtipo pequeño de estas vesículas (de 30 a 150 nm), producidos por una amplia variedad de tipos celulares incluyendo las neuronas, células tumorales, células epiteliales y células del sistema inmunológico. De entre estas últimas, las células presentadoras de antígeno se han caracterizado como productoras de exosomas con contenido variable, tanto en condiciones de reposo como en aquellas que derivan de su estimulación o maduración. En los últimos años el estudio de los exosomas ha aumentado debido a que se ha demostrado que dichas vesículas poseen propiedades inmunomoduladoras, razón por la que ostentan un gran potencial en aplicaciones de diagnóstico y desarrollo de terapias en diferentes patologías con componentes inflamatorios.
Referencias
Kreuger J, Phillipson M. Targeting vascular and leukocyte communication in angiogenesis, inflammation and fibrosis. Nature Rev Drug Discov. 2016;15(2):125-142. DOI: http://dx.doi.org/10.1038/nrd.2015.2
Andaloussi S, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nature Rev Drug Discov. 2013;12(5):347-357. DOI: http://dx.doi.org/10.1038/nrd3978
Mittelbrunn M, Gutierrez-Vázquez C, Villarroya-Beltri C, González S, Sanchez-Cabo F, Gonzalez MA, et al. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun. 2011;2:282. DOI: http://dx.doi.org/10.1038/ncomms1285
Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581-593. DOI: http://dx.doi.org/10.1038/nri2567
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654-659. DOI: http://dx.doi.org/10.1038/ncb1596
Pitt JM, Kroemer G, Zitvogel L. Extracellular vesicles: masters of intercellular communication and potential clinical interventions. J Clin Invest. 2016;126(4):1139-1143. DOI: http://dx.doi.org/10.1172/JCI87316
Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226-1232. DOI: http://dx.doi.org/10.1016/j.cell.2016.01.043
Sun D, Zhuang X, Zhang S, Deng ZB, Grizzle W, Miller D, et al. Exosomes are endogenous nanoparticles that can deliver biological information between cells. Adv Drug Deliv Rev. 2013;65(3):342-347. DOI: http://dx.doi.org/10.1016/j.addr.2012.07.002
Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin JP, et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest. 2010;120(2):457-471. DOI: http://dx.doi.org/10.1172/JCI40483
Gangoda L, Boukouris S, Liem M, Kalra H, Mathivanan S. Extracellular vesicles including exosomes are mediators of signal transduction: are they protective or pathogenic? Proteomics. 2015;15(2-3):260-271. DOI: http://dx.doi.org/10.1002/pmic.201400234
Zhang B, Yin Y, Lai RC, Lim SK. Immunotherapeutic potential of extracellular vesicles. Front Immunol. 2014;5:518. DOI: http://dx.doi.org/10.3389/fimmu.2014.00518
Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81(1):1-5. DOI: http://dx.doi.org/10.1189/jlb.0306164
Vivier E, Malissen B. Innate and adaptive immunity: specificities and signaling hierarchies revisited. Nat Immunol. 2005;6(1):17-21. DOI: http://dx.doi.org/10.1038/ni1153
Théry C, Amigorena S. The cell biology of antigen presentation in dendritic cells. Curr Opin Immunol. 2001;13(1):45-51. DOI: http://dx.doi.org/10.1016/S0952-7915(00)00180-1
Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W. Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol. 2015;40:72-81. DOI: http://dx.doi.org/10.1016/j.semcdb.2015.02.009
Chaput N, Thery C. Exosomes: immune properties and potential clinical implementations. Semin Immunopathol. 2011;33(5):419-440. DOI: http://dx.doi.org/10.1007/s00281-010-0233-9
Huang X, Yuan T, Tschannen M, Sun Z, Jacob H, Du M, et al. Characterization of human plasma-derived exosomal RNA by deep sequencing. BMC Genomics. 2013;14:319. DOI: http://dx.doi.org/10.1186/1471-2164-14-319
Koh W, Sheng CT, Tan B, Lee QY, Kuznetsov V, Kiang LS, et al. Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha. BMC Genomics. 2010;11(Suppl 1):S6. DOI: http://dx.doi.org/10.1186/1471-2164-11-S1-S6
Nolte-'t-Hoen EN, Buermans HP, Waasdorp M, Stoorvogel W, Wauben MH, ‘t-Hoen PA. Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res. 2012;40(18):9272-9285. DOI: http://dx.doi.org/10.1093/nar/gks658
Xiao D, Ohlendorf J, Chen Y, Taylor DD, Rai SN, Waigel S, et al. Identifying mRNA, microRNA and protein profiles of melanoma exosomes. PloS One. 2012;7(10):e46874. DOI: http://dx.doi.org/10.1371/journal.pone.0046874
Bhatt DM, Pandya-Jones A, Tong AJ, Barozzi I, Lissner MM, Natoli G, et al. Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell. 2012;150(2):279-290. DOI: http://dx.doi.org/10.1016/j.cell.2012.05.043
McDonald MK, Tian Y, Qureshi RA, Gormley M, Ertel A, Gao R, et al. Functional significance of macrophage-derived exosomes in inflammation and pain. Pain. 2014;155(8):1527-1539. DOI: http://dx.doi.org/10.1016/j.pain.2014.04.029
Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA. 2012;109(31):E2110-E2116. DOI: http://dx.doi.org/10.1073/pnas.1209414109
Stoorvogel W. Functional transfer of microRNA by exosomes. Blood. 2012;119(3):646-648. DOI: http://dx.doi.org/10.1182/blood-2011-11-389478
Squadrito ML, Baer C, Burdet F, Maderna C, Gilfillan GD, Lyle R, et al. Endogenous RNA modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep. 2014;8(5):1432-1446. DOI: http://dx.doi.org/10.1016/j.celrep.2014.07.035
Kosaka N, Iguchi H, Hagiwara K, Yoshioka Y, Takeshita F, Ochiya T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem. 2013;288(15):10849-10859. DOI: http://dx.doi.org/10.1074/jbc.M112.446831
Villarroya-Beltri C, Baixauli F, Gutiérrez-Vázquez C, Sánchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin Cancer Biol. 2014;28:3-13. DOI: http://dx.doi.org/10.1016/j.semcancer.2014.04.009
Koppers-Lalic D, Hackenberg M, Bijnsdorp IV, Van-Eijndhoven MA, Sadek P, Sie D, et al. Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Rep. 2014;8(6):1649-1658. DOI: http://dx.doi.org/10.1016/j.celrep.2014.08.027
Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol. 2009;11(9):1143-1149. DOI: http://dx.doi.org/10.1038/ncb1929
Zhang J, Li S, Lu L, Li M, Guo C, Yao J, et al. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics, Proteomics Bioinformatics. 2015;13(1):17-24. DOI: http://dx.doi.org/10.1016/j.gpb.2015.02.001
Dustin ML. Signaling at neuro/immune synapses. J Clin Invest. 2012;122(4):1149-1155. DOI: http://dx.doi.org/10.1172/JCI58705
McCall CE, El-Gazzar M, Liu T, Vachharajani V, Yoza B. Epigenetics, bioenergetics, and microRNA coordinate gene-specific reprogramming during acute systemic inflammation. J Leukoc Biol. 2011;90(3):439-446. DOI: http://dx.doi.org/10.1189/jlb.0211075
Batagov AO, Kurochkin IV. Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3'-untranslated regions. Biol Direct. 2013;8:12. DOI: http://dx.doi.org/10.1186/1745-6150-8-12
Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci USA. 2016;113(8):E968-E977. DOI: http://dx.doi.org/10.1073/pnas.1521230113
Mathivanan S, Fahner CJ, Reid GE, Simpson RJ. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res. 2012;40(Database issue):D1241-D1244. DOI: http://dx.doi.org/10.1093/nar/gkr828
Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, et al. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 2012;10(12):e1001450. DOI: http://dx.doi.org/10.1371/journal.pbio.1001450
Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255-289. DOI: http://dx.doi.org/10.1146/annurev-cellbio-101512-122326
Yáñez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:27066. DOI: http://dx.doi.org/10.3402/jev.v4.27066
Munich S, Sobo-Vujanovic A, Buchser WJ, Beer-Stolz D, Vujanovic NL. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology. 2012;1(7):1074-1083. DOI: http://dx.doi.org/10.4161/onci.20897
Simhadri VR, Reiners KS, Hansen HP, Topolar D, Simhadri VL, Nohroudi K, et al. Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function. PloS One. 2008;3(10):e3377. DOI: http://dx.doi.org/10.1371/journal.pone.0003377
Srinivasan S, Su M, Ravishankar S, Moore J, Head P, Dixon JB, et al. TLR-exosomes exhibit distinct kinetics and effector function. Sci Rep. 2017;7:41623. DOI: http://dx.doi.org/10.1038/srep41623
Montecalvo A, Shufesky WJ, Stolz DB, Sullivan MG, Wang Z, Divito SJ, et al. Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J Immunol. 2008;180(5):3081-3090. DOI: http://dx.doi.org/10.4049/jimmunol.180.5.3081
Qazi KR, Gehrmann U, Domange-Jordö E, Karlsson MC, Gabrielsson S. Antigen-loaded exosomes alone induce Th1-type memory through a B-cell-dependent mechanism. Blood. 2009;113(12):2673-2683. DOI: http://dx.doi.org/10.1182/blood-2008-04-153536
Théry C, Duban L, Segura E, Véron P, Lantz O, Amigorena S. Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol. 2002;3(12):1156-1162. DOI: http://dx.doi.org/10.1038/ni854
Segura E, Amigorena S, Théry C. Mature dendritic cells secrete exosomes with strong ability to induce antigen-specific effector immune responses. Blood Cells Mol Dis. 2005;35(2):89-93. DOI: http://dx.doi.org/10.1016/j.bcmd.2005.05.003
Théry C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, et al. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999;147(3):599-610. DOI: http://dx.doi.org/10.1083/jcb.147.3.599
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: http://dx.doi.org/10.1016/j.bcmd.2005.05.001
Segura E, Nicco C, Lombard B, Véron P, Raposo G, Batteux F, et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood. 2005;106(1):216-223. DOI: http://dx.doi.org/10.1182/blood-2005-01-0220
Utsugi-Kobukai S, Fujimaki H, Hotta C, Nakazawa M, Minami M. MHC class I-mediated exogenous antigen presentation by exosomes secreted from immature and mature bone marrow derived dendritic cells. Immunol Lett. 2003;89(2-3):125-131. DOI: http://dx.doi.org/10.1016/S0165-2478(03)00128-7
Luketic L, Delanghe J, Sobol PT, Yang P, Frotten E, Mossman KL, et al. Antigen presentation by exosomes released from peptide-pulsed dendritic cells is not suppressed by the presence of active CTL. J Immunol. 2007;179(8):5024-5032. DOI: http://dx.doi.org/10.4049/jimmunol.179.8.5024
Muntasell A, Berger AC, Roche PA. T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J. 2007;26(19):4263-4272. DOI: http://dx.doi.org/10.1038/sj.emboj.7601842
Admyre C, Bohle B, Johansson SM, Focke-Tejkl M, Valenta R, Scheynius A, et al. B cell-derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce TH2-like cytokines. J Allergy Clin Immunol. 2007;120(6):1418-1424. DOI: http://dx.doi.org/10.1016/j.jaci.2007.06.040
Hwang I, Shen X, Sprent J. Direct stimulation of naive T cells by membrane vesicles from antigen-presenting cells: distinct roles for CD54 and B7 molecules. Proc Natl Acad Sci USA. 2003;100(11):6670-6675. DOI: http://dx.doi.org/10.1073/pnas.1131852100
Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183(3):1161-72. DOI: http://dx.doi.org/10.1084/jem.183.3.1161
Vincent-Schneider H, Stumptner-Cuvelette P, Lankar D, Pain S, Raposo G, Benaroch P, et al. Exosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells. Int Immunol. 2002;14(7):713-722. DOI: http://dx.doi.org/10.1093/intimm/dxf048
Yin W, Ouyang S, Li Y, Xiao B, Yang H. Immature dendritic cell-derived exosomes: a promise subcellular vaccine for autoimmunity. Inflammation. 2013;36(1):232-240. DOI: http://dx.doi.org/10.1007/s10753-012-9539-1
Yang C, Robbins PD. Immunosuppressive exosomes: a new approach for treating arthritis. Int J Rheumatol. 2012;2012:573528. DOI: http://dx.doi.org/10.1155/2012/573528
Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med. 1998;4(5):594-600. DOI: http://dx.doi.org/10.1038/nm0598-594
Pitt JM, Charrier M, Viaud S, André F, Besse B, Chaput N, et al. Dendritic cell-derived exosomes as immunotherapies in the fight against cancer. J Immunol. 2014;193(3):1006-1011. DOI: http://dx.doi.org/10.4049/jimmunol.1400703
Robbins PD, Morelli AE. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol. 2014;14(3):195-208. DOI: http://dx.doi.org/10.1038/nri3622
Escudier B, Dorval T, Chaput N, Andre F, Caby MP, Novault S, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med. 2005;3(1):10. DOI: http://dx.doi.org/10.1186/1479-5876-3-10
Viaud S, Ploix S, Lapierre V, Thery C, Commere PH, Tramalloni D, et al. Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-gamma. J Immunother. 2011;34(1):65-75. DOI: http://dx.doi.org/10.1097/CJI.0b013e3181fe535b
Besse B, Charrier M, Lapierre V, Dansin E, Lantz O, Planchard D, et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology. 2016;5(4):e1071008. DOI: http://dx.doi.org/10.1080/2162402X.2015.1071008
Kim SH, Kim S, Evans CH, Ghivizzani SC, Oligino T, Robbins PD. Effective treatment of established murine collagen-induced arthritis by systemic administration of dendritic cells genetically modified to express IL-4. J Immunol. 2001;166(5):3499-3505. DOI: http://dx.doi.org/10.4049/jimmunol.166.5.3499
Kim SH, Kim S, Oligino TJ, Robbins PD. Effective treatment of established mouse collagen-induced arthritis by systemic administration of dendritic cells genetically modified to express FasL. Mol Ther. 2002;6(5):584-590. DOI: http://dx.doi.org/10.1006/mthe.2002.0712
Kim SH, Lechman ER, Bianco N, Menon R, Keravala A, Nash J, et al. Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J Immunol. 2005;174(10):6440-6448. DOI: http://dx.doi.org/10.4049/jimmunol.174.10.6440
Bianco NR, Kim SH, Ruffner MA, Robbins PD. Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase-positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models. Arthritis Rheum. 2009;60(2):380-389. DOI: http://dx.doi.org/10.1002/art.24229
Song J, Kim D, Han J, Kim Y, Lee M, Jin EJ. PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid arthritis. Clin Exp Med. 2015;15(1):121-126. DOI: http://dx.doi.org/10.1007/s10238-013-0271-4
Skriner K, Adolph K, Jungblut PR, Burmester GR. Association of citrullinated proteins with synovial exosomes. Arthritis Rheum. 2006;54(12):3809-3814. DOI: http://dx.doi.org/10.1002/art.22276
Perez-Hernandez J, Forner MJ, Pinto C, Chaves FJ, Cortes R, Redon J. Increased urinary exosomal microRNAs in patients with systemic lupus erythematosus. PloS One. 2015;10(9):e0138618. DOI: http://dx.doi.org/10.1371/journal.pone.0138618
Ichii O, Otsuka-Kanazawa S, Horino T, Kimura J, Nakamura T, Matsumoto M, et al. Decreased miR-26a expression correlates with the progression of podocyte injury in autoimmune glomerulonephritis. PloS One. 2014;9(10):e110383. DOI: http://dx.doi.org/10.1371/journal.pone.0110383
Sole C, Cortes-Hernandez J, Felip ML, Vidal M, Ordi-Ros J. miR-29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis. Nephrol Dial Transplant. 2015;30(9):1488-1496. DOI: http://dx.doi.org/10.1093/ndt/gfv128
Tandon M, Gallo A, Jang SI, Illei GG, Alevizos I. Deep sequencing of short RNA reveals novel microRNAs in minor salivary glands of patients with Sjögren's syndrome. Oral Dis. 2012;18(2):127-131. DOI: http://dx.doi.org/10.1111/j.1601-0825.2011.01849.x
Leoni G, Neumann PA, Kamaly N, Quiros M, Nishio H, Jones HR, et al. Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest. 2015;125(3):1215-1227. Disponible en: https://www.jci.org/articles/view/76693
Momen-Heravi F, Saha B, Kodys K, Catalano D, Satishchandran A, Szabo G. Increased number of circulating exosomes and their microRNA cargos are potential novel biomarkers in alcoholic hepatitis. J Trans Med. 2015;13:261. Disponible en: https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-015-0623-9
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