Mesenchymal stromal cell exosome-enhanced regulatory T-cell production through an antigen-presenting cell-mediated pathway
| Autor: | Sai Kiang Lim, Ronne Wee Yeh Yeo, Eugene Wei Kian Sim, Ruenn Chai Lai, Bin Zhang, Keh Chuang Chin |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Regulatory T cell T cell Immunology Antigen-Presenting Cells Graft vs Host Disease chemical and pharmacologic phenomena Mice SCID Exosomes Exosome T-Lymphocytes Regulatory 03 medical and health sciences medicine Immunology and Allergy Animals Humans IL-2 receptor Antigen-presenting cell Genetics (clinical) Transplantation Mice Inbred BALB C Chemistry CD28 FOXP3 Cell Polarity hemic and immune systems Mesenchymal Stem Cells Cell Biology medicine.disease Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Graft-versus-host disease Oncology Cancer research Female Signal Transduction |
| Zdroj: | Cytotherapy. 20(5) |
| ISSN: | 1477-2566 |
| Popis: | Background aims The immunomodulatory property of mesenchymal stromal cell (MSC) exosomes is well documented. On the basis of our previous report that MSC exosomes increased regulatory T-cell (Treg) production in mice with allogenic skin graft but not in ungrafted mice, we hypothesize that an activated immune system is key to exosome-mediated Treg production. Methods To test our hypothesis, MSC exosomes were incubated with mouse spleen CD4+ T cells that were activated with either anti-CD3/CD28 mAbs or allogenic antigen-presenting cell (APC)-enriched spleen CD11c+ cells to determine whether production of mouse CD4+CD25+ T cells or CD4+CD25+Foxp3+ Tregs could be induced. MSC exosomes were also administered to the lethal chimeric human-SCID mouse model of graft-versus-host disease (GVHD) in which human peripheral blood mononuclear cells were infused into irradiated NSG mice to induce GVHD. Results We report here that MSC exosome–induced production of CD4+CD25+ T cells or CD4+CD25+Foxp3+ Tregs from CD4+ T cells activated by allogeneic APC-enriched CD11C+ cells but not those activated by anti-CD3/CD28 mAbs. This induction was exosome- and APC dose–dependent. In the mouse GVHD model in which GVHD was induced by transplanted human APC-stimulated human anti-mouse CD4+ T cell effectors, MSC exosome alleviated GVHD symptoms and increased survival. Surviving exosome-treated mice had a significantly higher level of human CD4+CD25+CD127low/– Tregs than surviving mice treated with Etanercept, a tumor necrosis factor inhibitor. Conclusions MSC exosome enhanced Treg production in vitro and in vivo through an APC-mediated pathway. |
| Databáze: | OpenAIRE |
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