TY - JOUR
T1 - Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage
AU - Tung, Sim Lai
AU - Fanelli, Giorgia
AU - Matthews, Robert Ian
AU - Bazoer, Jordan
AU - Letizia, Marilena
AU - Vizcay-Barrena, Gema
AU - Faruqu, Farid N
AU - Philippeos, Christina
AU - Hannen, Rosalind
AU - Al-Jamal, Khuloud T
AU - Lombardi, Giovanna
AU - Smyth, Lesley Ann
N1 - Copyright © 2020 Tung, Fanelli, Matthews, Bazoer, Letizia, Vizcay-Barrena, Faruqu, Philippeos, Hannen, Al-Jamal, Lombardi and Smyth.
PY - 2020/5/20
Y1 - 2020/5/20
N2 - 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.
AB - 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.
KW - Regulatory T (Treg) cells
KW - allograft rejection
KW - cytokines
KW - extracellular vesicles
KW - miRNA – microRNA
UR - http://www.scopus.com/inward/record.url?scp=85085875414&partnerID=8YFLogxK
U2 - 10.3389/fcell.2020.00317
DO - 10.3389/fcell.2020.00317
M3 - Article
C2 - 32509778
SN - 2296-634X
VL - 8
SP - 317
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 317
ER -