Regulatory T Cell Extracellular Vesicles Modify T-Effector Cell Cytokine Production and Protect Against Human Skin Allograft Damage
| Autor: | Rosalind F. Hannen, Khuloud T. Al-Jamal, Giorgia Fanelli, Giovanna Lombardi, Lesley A. Smyth, Christina Philippeos, Farid N. Faruqu, Jordan Bazoer, Gema Vizcay-Barrena, Marilena Letizia, Robert Ian Matthews, Sim L. Tung |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Trogocytosis Regulatory T cell medicine.medical_treatment chemical and pharmacologic phenomena Cell and Developmental Biology 03 medical and health sciences 0302 clinical medicine Immune system medicine IL-2 receptor lcsh:QH301-705.5 Original Research Regulatory T (Treg) cells allograft rejection Chemistry Effector Cell Biology cytokines Cell biology 030104 developmental biology medicine.anatomical_structure Cytokine lcsh:Biology (General) 030220 oncology & carcinogenesis Humanized mouse miRNA – microRNA extracellular vesicles Intracellular Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology, Vol 8 (2020) Frontiers in Cell and Developmental Biology |
| ISSN: | 2296-634X |
| DOI: | 10.3389/fcell.2020.00317 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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