Regulatory T cell-derived extracellular vesicles modify dendritic cell function

Article


Tung, Sim L., Boardman, Dominic A., Sen, Monica, Letizia, Marilena, Peng, Qi, Cianci, Nicole, Dioni, Laura, Carlin, Leo M., Lechler, Robert, Bollati, Valentina, Lombardi, Giovanna and Smyth, L. 2018. Regulatory T cell-derived extracellular vesicles modify dendritic cell function. Scientific Reports. 8, p. 6065.
AuthorsTung, Sim L., Boardman, Dominic A., Sen, Monica, Letizia, Marilena, Peng, Qi, Cianci, Nicole, Dioni, Laura, Carlin, Leo M., Lechler, Robert, Bollati, Valentina, Lombardi, Giovanna and Smyth, L.
Abstract

Regulatory T cells (Treg) are a subpopulation of T cells that maintain tolerance to self and limit other immune responses. They achieve this through different mechanisms including the release of extracellular vesicles (EVs) such as exosomes as shown by us, and others. One of the ways that Treg derived EVs inhibit target cells such as effector T cells is via the transfer of miRNA. Another key target for the immunoregulatory function of Tregs is the dendritic cells (DCs). In this study we demonstrate directly, and for the first time, that miRNAs are transferred from Tregs to DCs via Treg derived EVs. In particular two miRNAs, namely miR-150-5p and miR-142-3p, were increased in DCs following their interaction with Tregs and Treg derived exosomes. One of the consequences for DCs following the acquisition of miRNAs contained in Treg derived EVs was the induction of a tolerogenic phenotype in these cells, with increased IL-10 and decreased IL-6 production being observed following LPS stimulation. Altogether our findings provide data to support the idea that intercellular transfer of miRNAs via EVs may be a novel mechanism by which Tregs regulate DC function and could represent a mechanism to inhibit immune reactions in tissues.

JournalScientific Reports
Journal citation8, p. 6065
ISSN2045-2322
Year2018
PublisherNature Publishing Group
Publisher's version
License
Publisher's version
License
Digital Object Identifier (DOI)doi:10.1038/s41598-018-24531-8
Web address (URL)https://doi.org/10.1038/s41598-018-24531-8
Publication dates
Online17 Apr 2018
Publication process dates
Deposited20 Apr 2018
Accepted03 Apr 2018
Accepted03 Apr 2018
FunderBritish Heart Foundation
Rosetrees Trust
Copyright information© 2018 The authors
LicenseCC BY 4.0
Permalink -

https://repository.uel.ac.uk/item/84862

  • 6
    total views
  • 32
    total downloads
  • 3
    views this month
  • 6
    downloads this month

Related outputs

Application of carbon nanotubes in cancer vaccines: Achievements, challenges and chances
Hassan, Hatem A.F.M., Diebold, Sandra S., Smyth, L., Walters, Adam A., Lombardi, Giovanna and Al-Jamal, Khuloud T. 2019. Application of carbon nanotubes in cancer vaccines: Achievements, challenges and chances. Journal of Controlled Release. 297, pp. 79-90.
Protease Activated Receptor 4 as a Novel Modulator of Regulatory T Cell Function
Peng, Q., Ratnasothy, K., Boardman, D. A., Jacob, J., Tung, S. T., McCluskey, D., Smyth, L., Lechler, R. I., Dorling, A. and Lombardi, G. 2019. Protease Activated Receptor 4 as a Novel Modulator of Regulatory T Cell Function. Frontiers in Immunology. 10 (Art. 1311).
Membrane radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice – a novel and universal approach
Faruqu, Farid N., Wang, Julie Tzu-Wen, Xu, Lizhou, McNickle, Luke, Chong, Eden Ming-Yiu, Walters, Adam, Gurney, Mark, Clayton, Aled, Smyth, L., Hider, Robert, Sosabowski, Jane and Al-Jamal, Khuloud T. 2019. Membrane radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice – a novel and universal approach. Theranostics. 9 (6), pp. 1666-1682.
Nox2 in regulatory T cells promotes angiotensin II–induced cardiovascular remodeling
Emmerson, Amber, Trevelin, Silvia Cellone, Mongue-Din, Heloise, Becker, Pablo D., Ortiz, Carla, Smyth, L., Peng, Qi, Elgueta, Raul, Sawyer, Greta, Ivetic, Aleksandar, Lechler, Robert I., Lombardi, Giovanna and Shah, Ajay M. 2018. Nox2 in regulatory T cells promotes angiotensin II–induced cardiovascular remodeling. Journal of Clinical Investigation. 128 (7), pp. 3088-3101.
Galectin-1 is required for the regulatory function of B cells
Alhabbab, R., Blair, P., Smyth, L., Ratnasothy, K., Peng, Q., Moreau, A., Lechler, R., Elgueta, R. and Lombardi, G. 2018. Galectin-1 is required for the regulatory function of B cells. Scientific Reports. 8 (2725).
Constitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance
Smyth, L., Meader, Lucy, Xiao, Fang, Woodward, Martin, Brady, Hugh J., Lechler, Robert and Lombardi, Giovanna 2017. Constitutive expression of the anti-apoptotic Bcl-2 family member A1 in murine endothelial cells leads to transplant tolerance. Clinical and Experimental Immunology. 188 (2), pp. 219-225.
Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy
Hassan, Hatem A.F.M., Smyth, L., Wang, Julie T.-W., Costa, Pedro M., Ratnasothy, Kulachelvy, Diebold, Sandra S., Lombardi, Giovanna and Al-Jamal, Khuloud T. 2016. Dual stimulation of antigen presenting cells using carbon nanotube-based vaccine delivery system for cancer immunotherapy. Biomaterials. 104, pp. 310-322.
Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation
Agarwal, Akansha, Fanelli, Giorgia, Letizia, Marilena, Tung, Sim Lai, Boardman, Dominic, Lechler, Robert, Lombardi, Giovanna and Smyth, L. 2014. Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation. Frontiers in Immunology. 5.
UK–Russia Researcher Links Workshop: extracellular vesicles – mechanisms of biogenesis and roles in disease pathogenesis, M.V. Lomonosov Moscow State University, Moscow, Russia, 1–5 March 2015
Kapustin, Alexander N., Kalinina, Natalia, Lopatina, Tatiana, Davidson, Sean M., Iraci, Nunzio, Tamkovich, Svetlana, Smyth, L., Ter-Ovanesyan, Dmitry, Evtushenko, Evgeniy G., Savelieva, Olga, Bertazzo, Sergio, Aushev, Vassiliy, Dragovic, Rebecca, Gracia, Tannia, Heck, Margarete, Parfyonova, Yelena V., Shanahan, Catherine M. and Tkachuk, Vsevolod 2015. UK–Russia Researcher Links Workshop: extracellular vesicles – mechanisms of biogenesis and roles in disease pathogenesis, M.V. Lomonosov Moscow State University, Moscow, Russia, 1–5 March 2015. Journal of Extracellular Vesicles. 4 (1), p. 28094.
Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model
Alhabbab, R., Blair, P., Elgueta, R., Stolarczyk, E., Marks, E., Becker, P. D., Ratnasothy, K., Smyth, L., Safinia, N., Sharif-Paghaleh, E., O’Connell, S., Noelle, R. J., Lord, G. M., Howard, J. K., Spencer, J., Lechler, R. I. and Lombardi, G. 2015. Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model. Scientific Reports. 5, p. 11554.
Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo
Hassan, Hatem A.F.M., Smyth, L., Rubio, Noelia, Ratnasothy, Kulachelvy, Wang, Julie T.-W., Bansal, Sukhvinder S., Summers, Huw D., Diebold, Sandra S., Lombardi, Giovanna and Al-Jamal, Khuloud T. 2016. Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo. Journal of Controlled Release. 225, pp. 205-216.
Continuous acquisition of MHC:peptide complexes by recipient cells contributes to the generation of anti-graft CD8+T cell immunity
Smyth, L., Lechler, Robert I and Lombardi, Giovanna 2016. Continuous acquisition of MHC:peptide complexes by recipient cells contributes to the generation of anti-graft CD8+T cell immunity. American Journal of Transplantation. 17 (1), pp. 60-68.
What Is Direct Allorecognition?
Boardman, Dominic A., Jacob, Jacinta, Smyth, L., Lombardi, Giovanna and Lechler, Robert I. 2016. What Is Direct Allorecognition? Current Transplantation Reports. 3 (4), pp. 275-283.
Treg therapy in transplantation a general overview
Romano, Marco, Tung, Sim Lai, Smyth, L. and Lombardi, Giovanna 2016. Treg therapy in transplantation a general overview. Transplant International. 30 (8), pp. 745-753.
Expression of a chimeric antigen receptor specific for donor HLA class I enhances the potency of human regulatory T cells in preventing human skin transplant rejection
Boardman, Dominic A., Philippeos, Christina, Fruhwirth, Gilbert O., Ibrahim, Mohammad A. A., Hannen, Rosalind F., Cooper, Dianne, Marelli-Berg, Federica M., Watt, Fiona M., Lechler, Robert I., Maher, John, Smyth, L. and Lombardi, Giovanna 2016. Expression of a chimeric antigen receptor specific for donor HLA class I enhances the potency of human regulatory T cells in preventing human skin transplant rejection. American Journal of Transplantation. 17 (4), pp. 931-943.