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

Frontiers in Cell and Developmental Biology
Sim L TungLesley A Smyth

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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Citations

Dec 1, 2020·American Journal of Reproductive Immunology : AJRI·Rodolfo R FavaroUdo R Markert
Dec 16, 2020·Cancers·Kevin Ho Wai YimRichard Chahwan
Dec 15, 2020·World Journal of Transplantation·Sotiris MastoridisAlberto Sanchez-Fueyo
Feb 16, 2021·The AAPS Journal·Akhil SrivastavaRajagopal Ramesh
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Apr 4, 2021·International Journal of Molecular Sciences·Enzo ManchonReem Al-Daccak
Jun 4, 2021·Cancer Letters·Pei-Pei Hou, Hang-Zi Chen

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Methods Mentioned

BETA
flow cytometry
FCS
ELISA
Xenograft
Fluorescence
confocal microscopy
PCR
electron microscopy

Clinical Trials Mentioned

NCT02129881
NCT02166177

Software Mentioned

NanoSight
FCAP Array
FIJI
ImageJ
Scaffold Proteome Software
GraphPad
NIS Elements
PRISM
FlowJo

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