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MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation
The molecules and mechanisms pertinent to the low immunogenicity of undifferentiated embryonic stem cells (ESCs) remain poorly understood. Here, we provide evidence that milk fat globule epidermal growth factor 8 (MFG-E8) is a vital mediator in this phenomenon and directly suppresses T cell immune r...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649138/ https://www.ncbi.nlm.nih.gov/pubmed/26455415 http://dx.doi.org/10.1016/j.stemcr.2015.09.005 |
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author | Tan, Yuan AlKhamees, Bodour Jia, Deyong Li, Li Couture, Jean-François Figeys, Daniel Jinushi, Masahisa Wang, Lisheng |
author_facet | Tan, Yuan AlKhamees, Bodour Jia, Deyong Li, Li Couture, Jean-François Figeys, Daniel Jinushi, Masahisa Wang, Lisheng |
author_sort | Tan, Yuan |
collection | PubMed |
description | The molecules and mechanisms pertinent to the low immunogenicity of undifferentiated embryonic stem cells (ESCs) remain poorly understood. Here, we provide evidence that milk fat globule epidermal growth factor 8 (MFG-E8) is a vital mediator in this phenomenon and directly suppresses T cell immune responses. MFG-E8 is enriched in undifferentiated ESCs but diminished in differentiated ESCs. Upregulation of MFG-E8 in ESCs increases the successful engraftment of both undifferentiated and differentiated ESCs across major histocompatibility complex barriers. MFG-E8 suppresses T cell activation/proliferation and inhibits Th1, Th2, and Th17 subpopulations while increasing regulatory T cell subsets. Neutralizing MFG-E8 substantially abrogates these effects, whereas addition of recombinant MFG-E8 to differentiated ESCs restores immunosuppression. Furthermore, we provide the evidence that MFG-E8 suppresses T cell activation and regulates T cell polarization by inhibiting PKCθ phosphorylation through the α3/5βV integrin receptor. Our findings offer an approach to facilitate transplantation acceptance. |
format | Online Article Text |
id | pubmed-4649138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-46491382015-12-11 MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation Tan, Yuan AlKhamees, Bodour Jia, Deyong Li, Li Couture, Jean-François Figeys, Daniel Jinushi, Masahisa Wang, Lisheng Stem Cell Reports Article The molecules and mechanisms pertinent to the low immunogenicity of undifferentiated embryonic stem cells (ESCs) remain poorly understood. Here, we provide evidence that milk fat globule epidermal growth factor 8 (MFG-E8) is a vital mediator in this phenomenon and directly suppresses T cell immune responses. MFG-E8 is enriched in undifferentiated ESCs but diminished in differentiated ESCs. Upregulation of MFG-E8 in ESCs increases the successful engraftment of both undifferentiated and differentiated ESCs across major histocompatibility complex barriers. MFG-E8 suppresses T cell activation/proliferation and inhibits Th1, Th2, and Th17 subpopulations while increasing regulatory T cell subsets. Neutralizing MFG-E8 substantially abrogates these effects, whereas addition of recombinant MFG-E8 to differentiated ESCs restores immunosuppression. Furthermore, we provide the evidence that MFG-E8 suppresses T cell activation and regulates T cell polarization by inhibiting PKCθ phosphorylation through the α3/5βV integrin receptor. Our findings offer an approach to facilitate transplantation acceptance. Elsevier 2015-10-08 /pmc/articles/PMC4649138/ /pubmed/26455415 http://dx.doi.org/10.1016/j.stemcr.2015.09.005 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Tan, Yuan AlKhamees, Bodour Jia, Deyong Li, Li Couture, Jean-François Figeys, Daniel Jinushi, Masahisa Wang, Lisheng MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation |
title | MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation |
title_full | MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation |
title_fullStr | MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation |
title_full_unstemmed | MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation |
title_short | MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation |
title_sort | mfg-e8 is critical for embryonic stem cell-mediated t cell immunomodulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649138/ https://www.ncbi.nlm.nih.gov/pubmed/26455415 http://dx.doi.org/10.1016/j.stemcr.2015.09.005 |
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