MFG-E8 is critical for embryonic stem cell-mediated T cell immunomodulation

6Citations
Citations of this article
22Readers
Mendeley users who have this article in their library.

Abstract

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.

Cite

CITATION STYLE

APA

Tan, Y., AlKhamees, B., Jia, D., Li, L., Couture, J. F., Figeys, D., … Wang, L. (2015). MFG-E8 is critical for embryonic stem cell-mediated T cell immunomodulation. Stem Cell Reports, 5(5), 741–752. https://doi.org/10.1016/j.stemcr.2015.09.005

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free