Embryonic stem cells (ESCs) possess certain immunomodulatory properties; the defined components in ESCs, however, are largely unknown. Based on proteomic database, I report here that milk fat globule epidermal growth factor 8 (MFG-E8) is a key component in ESCs to suppress T cell activation and regulate T cell polarization. MFG-E8 is enriched in undifferentiated ESCs while diminishing in differentiated ESCs. Neutralizing ESC-derived MFG-E8 substantially ameliorates the suppressive effects of ESCs on T cell activation and proliferation. Additionally, MFG-E8 in ESCs is capable of up-regulating T regulatory cells. I further prove that MFG-E8 suppresses T cell activation and regulates T cell polarization through inhibiting PKCθ phosphorylation. In vivo teratoma formation assay reveals an increase in ESC engraftments across allogeneic barriers with less immunologic rejection by up-regulation of MFG-E8 expression in ESCs, further validating the immunosuppressive properties of MFG-E8. Identifying an important immunoregulatory component in ESCs will greatly facilitate stem cell-based therapies.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/32188 |
| Date | January 2015 |
| Creators | Tan, Yuan |
| Contributors | Wang, Lisheng |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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