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

Stem Cell Reports. 2015 Nov 10;5(5):741-752. doi: 10.1016/j.stemcr.2015.09.005. Epub 2015 Oct 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Cells, Cultured
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / immunology*
  • Embryonic Stem Cells / transplantation
  • Histocompatibility*
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Milk Proteins / genetics
  • Milk Proteins / metabolism*
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Antigens, Surface
  • Mfge8 protein, mouse
  • Milk Proteins