An Updated View of the Importance of Vesicular Trafficking and Transport and Their Role in Immune-Mediated Diseases: Potential Therapeutic Interventions

Miguel A Ortega, Oscar Fraile-Martinez, Cielo Garcia-Montero, Miguel Angel Alvarez-Mon, Ana Maria Gomez-Lahoz, Agustin Albillos, Guillermo Lahera, Javier Quintero, Jorge Monserrat, Luis G Guijarro, Melchor Alvarez-Mon, Miguel A Ortega, Oscar Fraile-Martinez, Cielo Garcia-Montero, Miguel Angel Alvarez-Mon, Ana Maria Gomez-Lahoz, Agustin Albillos, Guillermo Lahera, Javier Quintero, Jorge Monserrat, Luis G Guijarro, Melchor Alvarez-Mon

Abstract

Cellular trafficking is the set of processes of distributing different macromolecules by the cell. This process is highly regulated in cells, involving a system of organelles (endomembranous system), among which are a great variety of vesicles that can be secreted from the cell, giving rise to different types of extracellular vesicles (EVs) that can be captured by other cells to modulate their function. The cells of the immune system are especially sensitive to this cellular traffic, producing and releasing different classes of EVs, especially in disease states. There is growing interest in this field due to the therapeutic and translational possibilities it offers. Different ways of taking advantage of the understanding of cell trafficking and EVs are being investigated, and their use as biomarkers or therapeutic targets is being investigated. The objective of this review is to collect the latest results and knowledge in this area with a specific focus on immune-mediated diseases. Although some promising results have been obtained, further knowledge is still needed, at both the basic and translational levels, to understand and modulate cellular traffic and EVs for better clinical management of these patients.

Keywords: cellular traffic; exosomes; extracellular vesicles; immune-mediated diseases; therapeutic applications.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Summary of the main parties involved in cellular and vesicular traffic. There is communication between the ER and the GA, where the vesicles are packed and classified, transporting different contents in both directions (anterograde and retrograde transport). Some of these vesicles are sent to the plasma membrane to be secreted by a process of constitutive or regulated exocytosis (mainly mediated by the SNARE complex). By endocytosis, different vesicles and substances from the medium are captured, entering the cell and forming the early endosome. The early endosome can recycle these components back to the cell exterior, send them to the GA, or give rise to a secondary endosome, also called multivesicular bodies (MVBs), as this structure contains multiple smaller vesicles known as intraluminal vesicles (ILVs). There is important communication between the GA and MVBs, yielding a bidirectional exchange of vesicles that can be secreted, giving rise to exosomes or becoming part of lysosomes for their subsequent degradation. Likewise, other types of extracellular vesicles, ectosomes or microvesicles (MVs), can be formed directly from the plasma membrane. It is noteworthy that each vesicle can have very diverse contents, including different types of proteins, lipids, and nucleic acids.
Figure 2
Figure 2
Overall summary of the therapeutic strategies currently pursued to limit the influence of high cellular traffic, production, release, and uptake in the IS. There are different approaches aimed at cell trafficking and its organelles, as well as at EVs, with some promising but still preclinical results. On the other hand, researchers are also beginning to design EVs that can be used for therapeutic purposes. In these cases, it is important to try to ensure their specificity and avoid their elimination by cells of the IS, so the selection of their membrane components should be oriented to this end. In the same way, modulating their contents and even adding a specific therapeutic agent could bring multiple benefits to the clinical management of IMIDs. For this, different approaches are being evaluated, such as modifying their content before their production (at the cellular level) or after being released by the cells, through chemical modifications.

References

    1. Overview of Intracellular Compartments and Trafficking Pathways—Madame Curie Bioscience Database—NCBI Bookshelf. [(accessed on 2 April 2022)]; Available online:
    1. Yarwood R., Hellicar J., Woodman P.G., Lowe M. Membrane trafficking in health and disease. Dis. Model. Mech. 2020;13:dmm043448. doi: 10.1242/dmm.043448.
    1. Howell G.J., Holloway Z.G., Cobbold C., Monaco A.P., Ponnambalam S. Cell Biology of Membrane Trafficking in Human Disease. Int. Rev. Cytol. 2006;252:1–69. doi: 10.1016/s0074-7696(06)52005-4.
    1. Wang X., Huang T., Bu G., Xu H. Dysregulation of protein trafficking in neurodegeneration. Mol. Neurodegener. 2014;9:31. doi: 10.1186/1750-1326-9-31.
    1. Juliano R.L., Carver K. Cellular uptake and intracellular trafficking of oligonucleotides. Adv. Drug Deliv. Rev. 2015;87:35–45. doi: 10.1016/j.addr.2015.04.005.
    1. Derby M.C., Gleeson P.A. New Insights into Membrane Trafficking and Protein Sorting. Int. Rev. Cytol. 2007;261:47–116. doi: 10.1016/s0074-7696(07)61002-x.
    1. Jackson C.L., Walch L., Verbavatz J.-M. Lipids and Their Trafficking: An Integral Part of Cellular Organization. Dev. Cell. 2016;39:139–153. doi: 10.1016/j.devcel.2016.09.030.
    1. Bagheri Y., Ali A.A., You M. Current Methods for Detecting Cell Membrane Transient Interactions. Front. Chem. 2020;8:603259. doi: 10.3389/fchem.2020.603259.
    1. Zaborowski M.P., Balaj L., Breakefield X.O., Lai C.P. Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study. Bioscience. 2015;65:783–797. doi: 10.1093/biosci/biv084.
    1. Yáñez-Mó M., Siljander P.R.-M., Andreu Z., Zavec A.B., Borràs F.E., Buzas E.I., Buzas K., Casal E., Cappello F., Carvalho J., et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles. 2015;4:27066. doi: 10.3402/jev.v4.27066.
    1. Shen Q., Wang Y.E., Palazzo A.F. Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection. J. Biol. Chem. 2021;297:100856. doi: 10.1016/j.jbc.2021.100856.
    1. Taguchi T., Mukai K. Innate immunity signalling and membrane trafficking. Curr. Opin. Cell Biol. 2019;59:1–7. doi: 10.1016/j.ceb.2019.02.002.
    1. Watkin L.B., Jessen B., Wiszniewski W., Vece T.J., Jan M., Sha Y., Thamsen M., Santos-Cortez R.L.P., Lee K., Gambin T., et al. COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nat. Genet. 2015;47:654–660. doi: 10.1038/ng.3279.
    1. Benado A., Nasagi-Atiya Y., Sagi-Eisenberg R. Protein trafficking in immune cells. Immunobiology. 2009;214:507–525. doi: 10.1016/j.imbio.2008.11.011.
    1. Manna P.T., Chiang S.C.C., Bryceson Y.T., Orange J.S., Ammann S. Editorial: Membrane Trafficking in Immunology—How Membrane Transport and Exocytosis Defects Underlie Immunodeficiencies. Front. Immunol. 2021;12:4024. doi: 10.3389/fimmu.2021.769815.
    1. Zundler S., Becker E., Schulze L.L., Neurath M.F. Immune cell trafficking and retention in inflammatory bowel disease: Mechanistic insights and therapeutic advances. Gut. 2019;68:1688–1700. doi: 10.1136/gutjnl-2018-317977.
    1. Hwang H., Kim H., Han G., Lee J., Kim K., Kwon I., Yang Y., Kim S. Extracellular Vesicles as Potential Therapeutics for Inflammatory Diseases. Int. J. Mol. Sci. 2021;22:5487. doi: 10.3390/ijms22115487.
    1. Lu M., Xing H., Xun Z., Yang T., Zhao X., Cai C., Wang D., Ding P. Functionalized extracellular vesicles as advanced therapeutic nanodelivery systems. Eur. J. Pharm. Sci. 2018;121:34–46. doi: 10.1016/j.ejps.2018.05.001.
    1. Westrate L.M., Lee J.E., Prinz W.A., Voeltz G.K. Form Follows Function: The Importance of Endoplasmic Reticulum Shape. Annu. Rev. Biochem. 2015;84:791–811. doi: 10.1146/annurev-biochem-072711-163501.
    1. Schwarz D.S., Blower M.D. The endoplasmic reticulum: Structure, function and response to cellular signaling. Cell. Mol. Life Sci. 2016;73:79–94. doi: 10.1007/s00018-015-2052-6.
    1. Huang S., Wang Y. Golgi structure formation, function, and post-translational modifications in mammalian cells. F1000Research. 2017;6:2050. doi: 10.12688/f1000research.11900.1.
    1. Li J., Ahat E., Wang Y. The Golgi Apparatus and Centriole. Results and Problems in Cell Differentiation. Volume 67. Springer; Cham, Switzerland: 2019. Golgi structure and function in health, stress, and diseases; pp. 441–485.
    1. Spang A. The Life Cycle of a Transport Vesicle. Cell. Mol. Life Sci. 2008;65:2781–2789. doi: 10.1007/S00018-008-8349-Y.
    1. Takahashi M., Nishiki T. Exocytosis. Tanpakushitsu Kakusan Koso. 1998;43:1761–1769. doi: 10.1016/B0-12-386860-2/00257-4.
    1. Liang K., Wei L., Chen L. Exocytosis, Endocytosis, and Their Coupling in Excitable Cells. Front. Mol. Neurosci. 2017;10:109. doi: 10.3389/fnmol.2017.00109.
    1. Pickett J.A., Edwardson J.M. Compound Exocytosis: Mechanisms and Functional Significance. Traffic. 2006;7:109–116. doi: 10.1111/j.1600-0854.2005.00372.x.
    1. Wu L.-G., Hamid E., Shin W., Chiang H.-C. Exocytosis and Endocytosis: Modes, Functions, and Coupling Mechanisms. Annu. Rev. Physiol. 2014;76:301–331. doi: 10.1146/annurev-physiol-021113-170305.
    1. Muro S. Alterations in Cellular Processes Involving Vesicular Trafficking and Implications in Drug Delivery. Biomimetics. 2018;3:19. doi: 10.3390/biomimetics3030019.
    1. Kumari S., Mg S., Mayor S. Endocytosis unplugged: Multiple ways to enter the cell. Cell Res. 2010;20:256–275. doi: 10.1038/cr.2010.19.
    1. Scott C.C., Vacca F., Gruenberg J. Endosome maturation, transport and functions. Semin. Cell Dev. Biol. 2014;31:2–10. doi: 10.1016/j.semcdb.2014.03.034.
    1. Huotari J., Helenius A. Endosome maturation. EMBO J. 2011;30:3481–3500. doi: 10.1038/emboj.2011.286.
    1. Piper R.C., Katzmann D.J. Biogenesis and Function of Multivesicular Bodies. Annu. Rev. Cell Dev. Biol. 2007;23:519–547. doi: 10.1146/annurev.cellbio.23.090506.123319.
    1. Ayloo S., Gu C. Transcytosis at the blood–brain barrier. Curr. Opin. Neurobiol. 2019;57:32–38. doi: 10.1016/j.conb.2018.12.014.
    1. Huang Y., Yin H., Li B., Wu Q., Liu Y., Poljak K., Maldutyte J., Tang X., Wang M., Wu Z., et al. An in vitro vesicle formation assay reveals cargo clients and factors that mediate vesicular trafficking. Proc. Natl. Acad. Sci. USA. 2021;118:e2101287118. doi: 10.1073/pnas.2101287118.
    1. Harris K.P., Littleton J.T. Vesicle Trafficking: A Rab Family Profile. Curr. Biol. 2011;21:R841–R843. doi: 10.1016/j.cub.2011.08.061.
    1. Koike S., Jahn R. SNAREs define targeting specificity of trafficking vesicles by combinatorial interaction with tethering factors. Nat. Commun. 2019;10:1608. doi: 10.1038/s41467-019-09617-9.
    1. Hofmann L., Ludwig S., Vahl J.M., Brunner C., Hoffmann T.K., Theodoraki M.-N. The Emerging Role of Exosomes in Diagnosis, Prognosis, and Therapy in Head and Neck Cancer. Int. J. Mol. Sci. 2020;21:4072. doi: 10.3390/ijms21114072.
    1. Boukouris S., Mathivanan S. Exosomes in bodily fluids are a highly stable resource of disease biomarkers. Proteom. Clin. Appl. 2015;9:358–367. doi: 10.1002/prca.201400114.
    1. Kalluri R. The biology and function of exosomes in cancer. J. Clin. Investig. 2016;126:1208–1215. doi: 10.1172/JCI81135.
    1. Zhang Y., Liu Y., Liu H., Tang W.H. Exosomes: Biogenesis, biologic function and clinical potential. Cell Biosci. 2019;9:19. doi: 10.1186/s13578-019-0282-2.
    1. Henne W.M., Buchkovich N.J., Emr S.D. The ESCRT Pathway. Dev. Cell. 2011;21:77–91. doi: 10.1016/j.devcel.2011.05.015.
    1. Hurley J.H. ESCRTs are everywhere. EMBO J. 2015;34:2398–2407. doi: 10.15252/embj.201592484.
    1. Kowal J., Tkach M., Théry C. Biogenesis and secretion of exosomes. Curr. Opin. Cell Biol. 2014;29:116–125. doi: 10.1016/j.ceb.2014.05.004.
    1. Minciacchi V.R., Freeman M.R., Di Vizio D. Extracellular Vesicles in Cancer: Exosomes, Microvesicles and the Emerging Role of Large Oncosomes. Semin. Cell Dev. Biol. 2015;40:41–51. doi: 10.1016/j.semcdb.2015.02.010.
    1. Ghossoub R., Lembo F., Rubio A., Gaillard C.B., Bouchet J., Vitale N., Slavík J., Machala M., Zimmermann P. Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2. Nat. Commun. 2014;5:3477. doi: 10.1038/ncomms4477.
    1. Anand S., Foot N., Ang C., Gembus K.M., Keerthikumar S., Adda C.G., Mathivanan S., Kumar S. Arrestin-Domain Containing Protein 1 (Arrdc1) Regulates the Protein Cargo and Release of Extracellular Vesicles. Proteomics. 2018;18:e1800266. doi: 10.1002/pmic.201800266.
    1. Juan T., Fürthauer M. Biogenesis and function of ESCRT-dependent extracellular vesicles. Semin. Cell Dev. Biol. 2018;74:66–77. doi: 10.1016/j.semcdb.2017.08.022.
    1. Adell M.A.Y., Vogel G.-F., Pakdel M., Müller M., Lindner H., Hess M., Teis D. Coordinated binding of Vps4 to ESCRT-III drives membrane neck constriction during MVB vesicle formation. J. Cell Biol. 2014;205:33–49. doi: 10.1083/jcb.201310114.
    1. Frankel E., Audhya A. ESCRT-dependent cargo sorting at multivesicular endosomes. Semin. Cell Dev. Biol. 2018;74:4–10. doi: 10.1016/j.semcdb.2017.08.020.
    1. Baietti M.F., Zhang Z., Mortier E., Melchior A., DeGeest G., Geeraerts A., Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., et al. Syndecan–syntenin–ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 2012;14:677–685. doi: 10.1038/ncb2502.
    1. Jankovičová J., Sečová P., Michalková K., Antalíková J. Tetraspanins, More than Markers of Extracellular Vesicles in Reproduction. Int. J. Mol. Sci. 2020;21:7568. doi: 10.3390/ijms21207568.
    1. Andreu Z., Yáñez-Mó M. Tetraspanins in Extracellular Vesicle Formation and Function. Front. Immunol. 2014;5:442. doi: 10.3389/fimmu.2014.00442.
    1. Gurung S., Perocheau D., Touramanidou L., Baruteau J. The exosome journey: From biogenesis to uptake and intracellular signalling. Cell Commun. Signal. 2021;19:47. doi: 10.1186/s12964-021-00730-1.
    1. Kenific C.M., Zhang H., Lyden D., Kenific C.M., Zhang H., Lyden D. An exosome pathway without an ESCRT. Cell Res. 2020;31:105–106. doi: 10.1038/s41422-020-00418-0.
    1. Kang T., Atukorala I., Mathivanan S. New Frontiers: Extracellular Vesicles. Volume 97. Springer; Cham, Switzerland: 2021. Biogenesis of extracellular vesicles; pp. 19–43. Subcellular Biochemistry.
    1. Hessvik N.P., Llorente A. Current knowledge on exosome biogenesis and release. Cell. Mol. Life Sci. 2018;75:193–208. doi: 10.1007/s00018-017-2595-9.
    1. Gagescu R. SNARE hypothesis 2000. Nat. Rev. Mol. Cell Biol. 2000;1:5. doi: 10.1038/35036010.
    1. Wang T., Li L., Hong W. SNARE proteins in membrane trafficking. Traffic. 2017;18:767–775. doi: 10.1111/tra.12524.
    1. Hong W., Lev S. Tethering the assembly of SNARE complexes. Trends Cell Biol. 2014;24:35–43. doi: 10.1016/j.tcb.2013.09.006.
    1. Hutagalung A.H., Novick P.J. Role of Rab GTPases in Membrane Traffic and Cell Physiology. Physiol. Rev. 2011;91:119–149. doi: 10.1152/physrev.00059.2009.
    1. Mathivanan S., Fahner C.J., Reid G.E., Simpson R.J. ExoCarta 2012: Database of exosomal proteins, RNA and lipids. Nucleic Acids Res. 2012;40:D1241–D1244. doi: 10.1093/nar/gkr828.
    1. Simpson R.J., Kalra H., Mathivanan S. ExoCarta as a resource for exosomal research. J. Extracell. Vesicles. 2012;1:18374. doi: 10.3402/jev.v1i0.18374.
    1. Keerthikumar S., Chisanga D., Ariyaratne D., Al Saffar H., Anand S., Zhao K., Samuel M., Pathan M., Jois M., Chilamkurti N., et al. ExoCarta: A Web-Based Compendium of Exosomal Cargo. J. Mol. Biol. 2016;428:688–692. doi: 10.1016/j.jmb.2015.09.019.
    1. Skotland T., Hessvik N.P., Sandvig K., Llorente A. Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology. J. Lipid Res. 2019;60:9–18. doi: 10.1194/jlr.R084343.
    1. Skotland T., Sandvig K., Llorente A. Lipids in exosomes: Current knowledge and the way forward. Prog. Lipid Res. 2017;66:30–41. doi: 10.1016/j.plipres.2017.03.001.
    1. Thakur B.K., Zhang H., Becker A., Matei I., Huang Y., Costa-Silva B., Zheng Y., Hoshino A., Brazier H., Xiang J., et al. Double-stranded DNA in exosomes: A novel biomarker in cancer detection. Cell Res. 2014;24:766–769. doi: 10.1038/cr.2014.44.
    1. Kahlert C., Melo S., Protopopov A., Tang J., Seth S., Koch M., Zhang J., Weitz J., Chin L., Futreal A., et al. Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer. J. Biol. Chem. 2014;289:3869–3875. doi: 10.1074/jbc.C113.532267.
    1. Guescini M., Genedani S., Stocchi V., Agnati L.F. Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J. Neural Transm. 2010;117:1. doi: 10.1007/s00702-009-0288-8.
    1. Lazo S., Hooten N.N., Green J., Eitan E., Mode N.A., Liu Q., Zonderman A.B., Ezike N., Mattson M.P., Ghosh P., et al. Mitochondrial DNA in extracellular vesicles declines with age. Aging Cell. 2021;20:e13283. doi: 10.1111/acel.13283.
    1. Arance E., Ramírez V., Rubio-Roldan A., Ocaña-Peinado F.M., Romero-Cachinero C., Jódar-Reyes A.B., Vazquez-Alonso F., Martinez-Gonzalez L.J., Alvarez-Cubero M.J. Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness. Cancers. 2021;14:199. doi: 10.3390/cancers14010199.
    1. Bellingham S.A., Coleman B.M., Hill A.F. Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic Acids Res. 2012;40:10937–10949. doi: 10.1093/nar/gks832.
    1. Chen F., Wang N., Tan H.-Y., Guo W., Zhang C., Feng Y. The functional roles of exosomes-derived long non-coding RNA in human cancer. Cancer Biol. Ther. 2019;20:583–592. doi: 10.1080/15384047.2018.1564562.
    1. Shtam T.A., Kovalev R.A., Varfolomeeva E.Y., Makarov E.M., Kil Y.V., Filatov M.V. Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun. Signal. 2013;11:88. doi: 10.1186/1478-811X-11-88.
    1. Urbanelli L., Buratta S., Sagini K., Ferrara G., Lanni M., Emiliani C. Exosome-based strategies for Diagnosis and Therapy. Recent Pat. CNS Drug Discov. 2015;10:10–27. doi: 10.2174/1574889810666150702124059.
    1. Wong C.H., Chen Y.-C. Clinical significance of exosomes as potential biomarkers in cancer. World J. Clin. Cases. 2019;7:171–190. doi: 10.12998/wjcc.v7.i2.171.
    1. Alghuthaymi M., Ahmad A., Khan Z., Khan S., Ahmed F., Faiz S., Nepovimova E., Kuča K., Abd-Elsalam K. Exosome/Liposome-like Nanoparticles: New Carriers for CRISPR Genome Editing in Plants. Int. J. Mol. Sci. 2021;22:7456. doi: 10.3390/ijms22147456.
    1. Chen Y., Li G., Liu M.-L. Microvesicles as Emerging Biomarkers and Therapeutic Targets in Cardiometabolic Diseases. Genom. Proteom. Bioinform. 2018;16:50–62. doi: 10.1016/j.gpb.2017.03.006.
    1. Camussi G., Deregibus M.C., Bruno S., Cantaluppi V., Biancone L. Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int. 2010;78:838–848. doi: 10.1038/ki.2010.278.
    1. Kalra H., Drummen G.P.C., Mathivanan S. Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. Int. J. Mol. Sci. 2016;17:170. doi: 10.3390/ijms17020170.
    1. Sedgwick A.E., Clancy J., Balmert M.O., D’Souza-Schorey C. Extracellular microvesicles and invadopodia mediate non-overlapping modes of tumor cell invasion. Sci. Rep. 2015;5:14748. doi: 10.1038/srep14748.
    1. Tricarico C., Clancy J., D’Souza-Schorey C. Biology and biogenesis of shed microvesicles. Small GTPases. 2017;8:220–232. doi: 10.1080/21541248.2016.1215283.
    1. Rauch S., Martin-Serrano J. Multiple Interactions between the ESCRT Machinery and Arrestin-Related Proteins: Implications for PPXY-Dependent Budding. J. Virol. 2011;85:3546–3556. doi: 10.1128/JVI.02045-10.
    1. Nabhan J.F., Hu R., Oh R.S., Cohen S.N., Lu Q. Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc. Natl. Acad. Sci. USA. 2012;109:4146–4151. doi: 10.1073/pnas.1200448109.
    1. Jackson C.E., Scruggs B.S., Schaffer J.E., Hanson P.I. Effects of Inhibiting VPS4 Support a General Role for ESCRTs in Extracellular Vesicle Biogenesis. Biophys. J. 2017;113:1342–1352. doi: 10.1016/j.bpj.2017.05.032.
    1. Wang T., Gilkes D.M., Takano N., Xiang L., Luo W., Bishop C.J., Chaturvedi P., Green J.J., Semenza G.L. Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis. Proc. Natl. Acad. Sci. USA. 2014;111:E3234–E3242. doi: 10.1073/pnas.1410041111.
    1. Choi D.-S., Kim D.-K., Kim Y.-K., Gho Y.S. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics. 2013;13:1554–1571. doi: 10.1002/pmic.201200329.
    1. Record M., Silvente-Poirot S., Poirot M., Wakelam M.J. Extracellular vesicles: Lipids as key components of their biogenesis and functions. J. Lipid Res. 2018;59:1316–1324. doi: 10.1194/jlr.E086173.
    1. Mulcahy L.A., Pink R.C., Carter D.R.F. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles. 2014;3:24641. doi: 10.3402/jev.v3.24641.
    1. Cocucci E., Racchetti G., Meldolesi J. Shedding microvesicles: Artefacts no more. Trends Cell Biol. 2009;19:43–51. doi: 10.1016/j.tcb.2008.11.003.
    1. Willms E., Cabañas C., Mäger I., Wood M.J.A., Vader P. Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression. Front. Immunol. 2018;9:738. doi: 10.3389/fimmu.2018.00738.
    1. Nawaz M., Shah N., Zanetti B.R., Maugeri M., Silvestre R.N., Fatima F., Neder L., Valadi H. Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair. Cells. 2018;7:167. doi: 10.3390/cells7100167.
    1. Panfoli I., Santucci L., Bruschi M., Petretto A., Calzia D., Ramenghi L.A., Ghiggeri G.M., Candiano G. Microvesicles as promising biological tools for diagnosis and therapy. Expert Rev. Proteom. 2018;15:801–808. doi: 10.1080/14789450.2018.1528149.
    1. Lundström A., Mobarrez F., Rooth E., Thålin C., von Arbin M., Henriksson P., Gigante B., Laska A.-C., Wallén H. Prognostic Value of Circulating Microvesicle Subpopulations in Ischemic Stroke and TIA. Transl. Stroke Res. 2020;11:708–719. doi: 10.1007/s12975-019-00777-w.
    1. Poon I.K.H., Parkes M.A.F., Jiang L., Atkin-Smith G.K., Tixeira R., Gregory C.D., Ozkocak D.C., Rutter S.F., Caruso S., Santavanond J.P., et al. Moving beyond size and phosphatidylserine exposure: Evidence for a diversity of apoptotic cell-derived extracellular vesicles in vitro. J. Extracell. Vesicles. 2019;8:1608786. doi: 10.1080/20013078.2019.1608786.
    1. Akers J.C., Gonda D., Kim R., Carter B.S., Chen C.C. Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neuro-Oncol. 2013;113:1–11. doi: 10.1007/s11060-013-1084-8.
    1. Charras G.T., Yarrow J.C., Horton M.A., Mahadevan L., Mitchison T.J. Non-equilibration of hydrostatic pressure in blebbing cells. Nature. 2005;435:365–369. doi: 10.1038/nature03550.
    1. Tixeira R., Phan T.K., Caruso S., Shi B., Atkin-Smith G.K., Nedeva C., Chow J.D.Y., Puthalakath H., Hulett M.D., Herold M., et al. ROCK1 but not LIMK1 or PAK2 is a key regulator of apoptotic membrane blebbing and cell disassembly. Cell Death Differ. 2019;27:102–116. doi: 10.1038/s41418-019-0342-5.
    1. Atkin-Smith G.K., Tixeira R., Paone S., Mathivanan S., Collins C., Liem M., Goodall K., Ravichandran K., Hulett M., Poon I.K. A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure. Nat. Commun. 2015;6:7439. doi: 10.1038/ncomms8439.
    1. Poon I., Chiu Y.-H., Armstrong A.J., Kinchen J., Juncadella I.J., Bayliss D.A., Ravichandran K. Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature. 2014;507:329–334. doi: 10.1038/nature13147.
    1. Santavanond J.P., Rutter S.F., Atkin-Smith G.K., Poon I.K.H. Apoptotic Bodies: Mechanism of Formation, Isolation and Functional Relevance. Subcell. Biochem. 2021;97:61–88. doi: 10.1007/978-3-030-67171-6_4.
    1. Atkin-Smith G.K., Poon I.K. Disassembly of the Dying: Mechanisms and Functions. Trends Cell Biol. 2016;27:151–162. doi: 10.1016/j.tcb.2016.08.011.
    1. Kaul Z., Chakrabarti O. Tumor susceptibility gene 101 regulates predisposition to apoptosis via ESCRT machinery accessory proteins. Mol. Biol. Cell. 2017;28:2106–2122. doi: 10.1091/mbc.e16-12-0855.
    1. Battistelli M., Falcieri E. Apoptotic Bodies: Particular Extracellular Vesicles Involved in Intercellular Communication. Biology. 2020;9:21. doi: 10.3390/biology9010021.
    1. Kourtzelis I., Hajishengallis G., Chavakis T. Phagocytosis of Apoptotic Cells in Resolution of Inflammation. Front. Immunol. 2020;11:553. doi: 10.3389/fimmu.2020.00553.
    1. Wickman G., Julian L., Olson M.F. How apoptotic cells aid in the removal of their own cold dead bodies. Cell Death Differ. 2012;19:735–742. doi: 10.1038/cdd.2012.25.
    1. Xu X., Lai Y., Hua Z.-C. Apoptosis and apoptotic body: Disease message and therapeutic target potentials. Biosci. Rep. 2019;39:BSR20180992. doi: 10.1042/BSR20180992.
    1. Lu M., DiBernardo E., Parks E., Fox H., Zheng S.-Y., Wayne E. The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Autoimmune Disorders. Front. Immunol. 2021;12:566299. doi: 10.3389/fimmu.2021.566299.
    1. Majdan M. Immune-Mediated Inflammatory Diseases and Accompanying Comorbidities. Wiad Lek. 2016;69:611–615.
    1. Rahman P., Inman R., El-Gabalawy H., Krause D.O. Pathophysiology and Pathogenesis of Immune-Mediated Inflammatory Diseases: Commonalities and Differences. J. Rheumatol. Suppl. 2010;85:11–26. doi: 10.3899/jrheum.091462.
    1. Williams J.P., Meyers J.A. Immune-Mediated Inflammatory Disorders (I.M.I.D.s): The Economic and Clinical Costs. Am. J. Manag. Care. 2002;21:S664–S681.
    1. McInnes I.B., Gravallese E.M. Immune-mediated inflammatory disease therapeutics: Past, present and future. Nat. Rev. Immunol. 2021;21:680–686. doi: 10.1038/s41577-021-00603-1.
    1. Unanue E.R., Urano F. Endoplasmic Reticulum: An Interface Between the Immune System and Metabolism. Diabetes. 2013;63:48–49. doi: 10.2337/db13-1478.
    1. Lerner A.G., Upton J.-P., Praveen P., Ghosh R., Nakagawa Y., Igbaria A., Shen S., Nguyen V., Backes B.J., Heiman M., et al. IRE1α Induces Thioredoxin-Interacting Protein to Activate the NLRP3 Inflammasome and Promote Programmed Cell Death under Irremediable ER Stress. Cell Metab. 2012;16:250–264. doi: 10.1016/j.cmet.2012.07.007.
    1. Iwasaki Y., Suganami T., Hachiya R., Shirakawa I., Kim-Saijo M., Tanaka M., Hamaguchi M., Takai-Igarashi T., Nakai M., Miyamoto Y., et al. Activating Transcription Factor 4 Links Metabolic Stress to Interleukin-6 Expression in Macrophages. Diabetes. 2014;63:152–161. doi: 10.2337/db13-0757.
    1. Tao Y., Yang Y., Zhou R., Gong T. Golgi Apparatus: An Emerging Platform for Innate Immunity. Trends Cell Biol. 2020;30:467–477. doi: 10.1016/j.tcb.2020.02.008.
    1. Fritzler M.J., Etherington J., Sokoluk C., Kinsella T.D., Valencia D.W. Antibodies from patients with autoimmune disease react with a cytoplasmic antigen in the Golgi apparatus. J. Immunol. 1984;132:2904–2908.
    1. Logan M.R., Odemuyiwa S.O., Moqbel R. Understanding Exocytosis in Immune and Inflammatory Cells: The Molecular Basis of Mediator Secretion. J. Allergy Clin. Immunol. 2003;111:923–932. doi: 10.1016/S0091-6749(03)80114-8.
    1. Ding X., Xiang S. Endocytosis and human innate immunity. J. Immunol. Sci. 2018;2:65–70. doi: 10.29245/2578-3009/2018/1.1121.
    1. Watts C. The endosome–lysosome pathway and information generation in the immune system. Biochim. Biophys. Acta (BBA) Proteins Proteom. 2012;1824:14–21. doi: 10.1016/j.bbapap.2011.07.006.
    1. Cuesta C.M., Guerri C., Ureña J., Pascual M. Role of Microbiota-Derived Extracellular Vesicles in Gut-Brain Communication. Int. J. Mol. Sci. 2021;22:4235. doi: 10.3390/ijms22084235.
    1. Regev-Rudzki N., Michaeli S., Torrecilhas A.C. Editorial: Extracellular Vesicles in Infectious Diseases. Front. Cell. Infect. Microbiol. 2021;11:430. doi: 10.3389/fcimb.2021.697919.
    1. Chang W.-H., Cerione R.A., Antonyak M.A. Extracellular Vesicles and Their Roles in Cancer Progression. Cancer Cell Signal. 2020;2174:143–170. doi: 10.1007/978-1-0716-0759-6_10.
    1. Vatter F.A.P., Cioffi M., Hanna S.J., Castarede I., Caielli S., Pascual V., Matei I., Lyden D. Extracellular vesicle– and particle-mediated communication shapes innate and adaptive immune responses. J. Exp. Med. 2021;218:e20202579. doi: 10.1084/jem.20202579.
    1. Grange C., Camussi G. Immunosuppressive role of extracellular vesicles: HLA-G, an important player. Ann. Transl. Med. 2017;5:223. doi: 10.21037/atm.2017.03.61.
    1. Cho K., Kook H., Kang S., Lee J. Study of immune-tolerized cell lines and extracellular vesicles inductive environment promoting continuous expression and secretion of HLA-G from semiallograft immune tolerance during pregnancy. J. Extracell. Vesicles. 2020;9:1795364. doi: 10.1080/20013078.2020.1795364.
    1. Marar C., Starich B., Wirtz D. Extracellular vesicles in immunomodulation and tumor progression. Nat. Immunol. 2021;22:560–570. doi: 10.1038/s41590-021-00899-0.
    1. Robbins P.D., Morelli A.E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 2014;14:195–208. doi: 10.1038/nri3622.
    1. Schioppo T., Ubiali T., Ingegnoli F., Bollati V., Caporali R. The role of extracellular vesicles in rheumatoid arthritis: A systematic review. Clin. Rheumatol. 2021;40:3481–3497. doi: 10.1007/s10067-021-05614-w.
    1. Fu H., Hu D., Zhang L., Tang P. Role of extracellular vesicles in rheumatoid arthritis. Mol. Immunol. 2018;93:125–132. doi: 10.1016/j.molimm.2017.11.016.
    1. Valter M., Verstockt S., Ferreiro J.A.F., Cleynen I. Extracellular Vesicles in Inflammatory Bowel Disease: Small Particles, Big Players. J. Crohn’s Colitis. 2020;15:499–510. doi: 10.1093/ecco-jcc/jjaa179.
    1. Shen Q., Huang Z., Yao J., Jin Y. Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease. J. Adv. Res. 2022;37:221–233. doi: 10.1016/j.jare.2021.07.002.
    1. Ivanov A.I. Pharmacological Inhibitors of Exocytosis and Endocytosis: Novel Bullets for Old Targets. Methods Mol. Biol. 2014;1174:3–18. doi: 10.1007/978-1-4939-0944-5_1.
    1. Harisa G.I., Faris T.M. Direct Drug Targeting into Intracellular Compartments: Issues, Limitations, and Future Outlook. J. Membr. Biol. 2019;252:527–539. doi: 10.1007/s00232-019-00082-5.
    1. Li A., Song N.-J., Riesenberg B.P., Li Z. The Emerging Roles of Endoplasmic Reticulum Stress in Balancing Immunity and Tolerance in Health and Diseases: Mechanisms and Opportunities. Front. Immunol. 2020;10:3154. doi: 10.3389/fimmu.2019.03154.
    1. Zappa F., Failli M., De Matteis M.A. The Golgi complex in disease and therapy. Curr. Opin. Cell Biol. 2018;50:102–116. doi: 10.1016/j.ceb.2018.03.005.
    1. Patra M.C., Achek A., Kim G.-Y., Panneerselvam S., Shin H.-J., Baek W.-Y., Lee W.H., Sung J., Jeong U., Cho E.-Y., et al. A Novel Small-Molecule Inhibitor of Endosomal TLRs Reduces Inflammation and Alleviates Autoimmune Disease Symptoms in Murine Models. Cells. 2020;9:1648. doi: 10.3390/cells9071648.
    1. Bonam S.R., Wang F., Muller S. Lysosomes as a therapeutic target. Nat. Rev. Drug Discov. 2019;18:923–948. doi: 10.1038/s41573-019-0036-1.
    1. Choudhuri K., Llodrá J., Roth E.W., Tsai J., Gordo S., Wucherpfennig K.W., Kam L.C., Stokes D.L., Dustin M.L. Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature. 2014;507:118–123. doi: 10.1038/nature12951.
    1. Catalano M., O’Driscoll L. Inhibiting extracellular vesicles formation and release: A review of EV inhibitors. J. Extracell. Vesicles. 2020;9:1703244. doi: 10.1080/20013078.2019.1703244.
    1. Menck K., Sönmezer C., Worst T.S., Schulz M., Dihazi G.H., Streit F., Erdmann G., Kling S., Boutros M., Binder C., et al. Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane. J. Extracell. Vesicles. 2017;6:1378056. doi: 10.1080/20013078.2017.1378056.
    1. Gon Y., Maruoka S., Inoue T., Kuroda K., Yamagishi K., Kozu Y., Shikano S., Soda K., Lötvall J., Hashimoto S. Selective release of miRNAs via extracellular vesicles is associated with house-dust mite allergen-induced airway inflammation. Clin. Exp. Allergy. 2017;47:1586–1598. doi: 10.1111/cea.13016.
    1. Morelli A.E., Larregina A.T., Shufesky W.J., Sullivan M.L.G., Stolz D.B., Papworth G.D., Zahorchak A.F., Logar A.J., Wang Z., Watkins S.C., et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood. 2004;104:3257–3266. doi: 10.1182/blood-2004-03-0824.
    1. Szondy Z., Garabuczi É., Joós G., Tsay G.J., Sarang Z. Impaired Clearance of Apoptotic Cells in Chronic Inflammatory Diseases: Therapeutic Implications. Front. Immunol. 2014;5:354. doi: 10.3389/fimmu.2014.00354.
    1. Simon H.-U. Targeting apoptosis in the control of inflammation. Eur. Respir. J. 2003;22((Suppl. 44)):20s–21s. doi: 10.1183/09031936.03.00000603b.
    1. Phan T.K., Ozkocak D.C., Poon I.K.H. Unleashing the therapeutic potential of apoptotic bodies. Biochem. Soc. Trans. 2020;48:2079–2088. doi: 10.1042/BST20200225.
    1. Zhou H., Ni W.-J., Meng X.-M., Tang L.-Q. MicroRNAs as Regulators of Immune and Inflammatory Responses: Potential Therapeutic Targets in Diabetic Nephropathy. Front. Cell Dev. Biol. 2021;8:1837. doi: 10.3389/fcell.2020.618536.
    1. O’Brien K., Breyne K., Ughetto S., Laurent L.C., Breakefield X.O. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat. Rev. Mol. Cell Biol. 2020;21:585–606. doi: 10.1038/s41580-020-0251-y.
    1. Murphy D.E., De Jong O.G., Brouwer M., Wood M.J., Lavieu G., Schiffelers R.M., Vader P. Extracellular vesicle-based therapeutics: Natural versus engineered targeting and trafficking. Exp. Mol. Med. 2019;51:1–12. doi: 10.1038/s12276-019-0223-5.
    1. Gowen A., Shahjin F., Chand S., Odegaard K.E., Yelamanchili S.V. Mesenchymal Stem Cell-Derived Extracellular Vesicles: Challenges in Clinical Applications. Front. Cell Dev. Biol. 2020;8:149. doi: 10.3389/fcell.2020.00149.
    1. Shigemoto-Kuroda T., Oh J.Y., Kim D.-K., Jeong H.J., Park S.Y., Lee H.J., Park J.W., Kim T.W., An S.Y., Prockop D.J., et al. MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis. Stem Cell Rep. 2017;8:1214–1225. doi: 10.1016/j.stemcr.2017.04.008.
    1. Dabrowska S., Andrzejewska A., Janowski M., Lukomska B. Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cells and Extracellular Vesicles: Therapeutic Outlook for Inflammatory and Degenerative Diseases. Front. Immunol. 2021;11:591065. doi: 10.3389/fimmu.2020.591065.
    1. Wang J., Xia J., Huang R., Hu Y., Fan J., Shu Q., Xu J. Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization. Stem Cell Res. Ther. 2020;11:424. doi: 10.1186/s13287-020-01937-8.
    1. Abreu S.C., Lopes-Pacheco M., Weiss D.J., Rocco P.R.M. Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Lung Diseases: Current Status and Perspectives. Front. Cell Dev. Biol. 2021;9:97. doi: 10.3389/fcell.2021.600711.
    1. Antimisiaris S.G., Mourtas S., Marazioti A. Exosomes and Exosome-Inspired Vesicles for Targeted Drug Delivery. Pharmaceutics. 2018;10:218. doi: 10.3390/pharmaceutics10040218.
    1. Kalinec G.M., Gao L., Cohn W., Whitelegge J.P., Faull K.F., Kalinec F. Extracellular Vesicles from Auditory Cells as Nanocarriers for Anti-inflammatory Drugs and Pro-resolving Mediators. Front. Cell. Neurosci. 2019;13:530. doi: 10.3389/fncel.2019.00530.
    1. Zhuang X., Xiang X., Grizzle W., Sun D., Zhang S., Axtell R.C., Ju S., Mu J., Zhang L., Steinman L., et al. Treatment of Brain Inflammatory Diseases by Delivering Exosome Encapsulated Anti-inflammatory Drugs from the Nasal Region to the Brain. Mol. Ther. 2011;19:1769–1779. doi: 10.1038/mt.2011.164.
    1. Kim I.-K., Kim S.-H., Choi S.-M., Youn B.-S., Kim H.-S. Extracellular Vesicles as Drug Delivery Vehicles for Rheumatoid Arthritis. Curr. Stem Cell Res. Ther. 2016;11:329–342. doi: 10.2174/1574888X11666151203223251.
    1. Chen Z., Wang H., Xia Y., Yan F., Lu Y. Therapeutic Potential of Mesenchymal Cell–Derived miRNA-150-5p–Expressing Exosomes in Rheumatoid Arthritis Mediated by the Modulation of MMP14 and VEGF. J. Immunol. 2018;201:2472–2482. doi: 10.4049/jimmunol.1800304.
    1. Casella G., Colombo F., Finardi A., Descamps H., Ill-Raga G., Spinelli A.E., Podini P., Bastoni M., Martino G., Muzio L., et al. Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis. Mol. Ther. 2018;26:2107–2118. doi: 10.1016/j.ymthe.2018.06.024.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel