MFG-E8 Is Critical for Embryonic Stem Cell-Mediated T Cell Immunomodulation

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...

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Main Authors: Tan, Yuan, AlKhamees, Bodour, Jia, Deyong, Li, Li, Couture, Jean-François, Figeys, Daniel, Jinushi, Masahisa, Wang, Lisheng
Format: Online
Language:English
Published: Elsevier 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649138/
id pubmed-4649138
recordtype oai_dc
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 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/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Tan, Yuan
AlKhamees, Bodour
Jia, Deyong
Li, Li
Couture, Jean-François
Figeys, Daniel
Jinushi, Masahisa
Wang, Lisheng
spellingShingle 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
author_facet Tan, Yuan
AlKhamees, Bodour
Jia, Deyong
Li, Li
Couture, Jean-François
Figeys, Daniel
Jinushi, Masahisa
Wang, Lisheng
author_sort Tan, Yuan
title 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_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_sort mfg-e8 is critical for embryonic stem cell-mediated t cell immunomodulation
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.
publisher Elsevier
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649138/
_version_ 1613502638237679616

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