T regulatory cells-derived extracellular vesicles and their contribution to the generation of immune tolerance

Carolina Rojas, Mauricio Campos-Mora, Ignacio Cárcamo, Natalia Villalón, Ahmed Elhusseiny, Pamina Contreras-Kallens, Aarón Refisch, Felipe Gálvez-Jirón, Ivana Emparán, Andro Montoya-Riveros, Rolando Vernal, Karina Pino-Lagos*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations


T regulatory (Treg) cells have a major role in the maintenance of immune tolerance against self and foreign antigens through the control of harmful inflammation. Treg cells exert immunosuppressive function by several mechanisms, which can be distinguished as contact dependent or independent. Recently, the secretion of extracellular vesicles (EVs) by Treg cells has been reported as a novel suppressive mechanism capable of modulating immunity in a cell-contact independent and targeted manner, which has been identified in different pathologic scenarios. EVs are cell-derived membranous structures involved in physiologic and pathologic processes through protein, lipid, and genetic material exchange, which allow intercellular communication. In this review, we revise and discuss current knowledge on Treg cells-mediated immune tolerance giving special attention to the production and release of EVs. Multiple studies support that Treg cells-derived EVs represent a refined intercellular exchange device with the capacity of modulating immune responses, thus creating a tolerogenic microenvironment in a cell-free manner. The mechanisms proposed encompass miRNAs-induced gene silencing, the action of surface proteins and the transmission of enzymes. These observations gain relevance by the fact that Treg cells are susceptible to converting into effector T cells after exposition to inflammatory environments. Yet, in contrast to their cells of origin, EVs are unlikely to be modified under inflammatory conditions, highlighting the advantage of their use. Moreover, we speculate in the possibility that Treg cells may contribute to infectious tolerance via vesicle secretion, intervening with CD4+ T cells differentiation and/or stability.

Original languageEnglish
Pages (from-to)813-824
Number of pages12
JournalJournal of Leukocyte Biology
Issue number3
StatePublished - 1 Sep 2020

Bibliographical note

Funding Information:
This work was financially supported by FONDECYT (nos. 1160347 and 1181780), and the National Scholarship CONICYT granted to C.R. (no. 2110841).

Publisher Copyright:
©2020 Society for Leukocyte Biology


  • T regulatory cells
  • extracellular vesicles
  • tolerance


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