Stem Cell Reports
Volume 5, Issue 5, 10 November 2015, Pages 741-752
Journal home page for Stem Cell Reports

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

https://doi.org/10.1016/j.stemcr.2015.09.005Get rights and content
Under a Creative Commons license
open access

Highlights

  • MFG-E8 is enriched in undifferentiated but diminished in differentiated ESCs

  • MFG-E8 promotes allogeneic engraftment of ESC-derived tissues across the MHC barrier

  • ESC-produced MFG-E8 inhibits Th1/Th2/Th17 while promoting regulatory T cells

  • MFG-E8 modulates T cell polarization via inhibiting PKCθ phosphorylation

Summary

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.

Cited by (0)

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).