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Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage

Research output: Contribution to journalArticle

Sim Lai Tung, Giorgia Fanelli, Robert Ian Matthews, Jordan Bazoer, Marilena Letizia, Gema Vizcay-Barrena, Farid N Faruqu, Christina Philippeos, Rosalind Hannen, Khuloud T Al-Jamal, Giovanna Lombardi, Lesley Ann Smyth

Original languageEnglish
Article number317
Pages (from-to)317
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Published20 May 2020

Bibliographical note

Copyright © 2020 Tung, Fanelli, Matthews, Bazoer, Letizia, Vizcay-Barrena, Faruqu, Philippeos, Hannen, Al-Jamal, Lombardi and Smyth.

King's Authors

Abstract

Regulatory T cells (Tregs) are a subpopulation of CD4+ T cells with a fundamental role in maintaining immune homeostasis and inhibiting unwanted immune responses using several different mechanisms. Recently, the intercellular transfer of molecules between Tregs and their target cells has been shown via trogocytosis and the release of small extracellular vesicles (sEVs). In this study, CD4+CD25+CD127lo human Tregs were found to produce sEVs capable of inhibiting the proliferation of effector T cells (Teffs) in a dose dependent manner. These vesicles also modified the cytokine profile of Teffs leading to an increase in the production of IL-4 and IL-10 whilst simultaneously decreasing the levels of IL-6, IL-2, and IFNγ. MicroRNAs found enriched in the Treg EVs were indirectly linked to the changes in the cytokine profile observed. In a humanized mouse skin transplant model, human Treg derived EVs inhibited alloimmune-mediated skin tissue damage by limiting immune cell infiltration. Taken together, Treg sEVs may represent an exciting cell-free therapy to promote transplant survival.

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