| First Author | Freywald A | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 7 | Pages | 4066-74 |
| PubMed ID | 16547242 | Mgi Jnum | J:129912 |
| Mgi Id | MGI:3770376 | Doi | 10.4049/jimmunol.176.7.4066 |
| Citation | Freywald A, et al. (2006) EphA receptors inhibit anti-CD3-induced apoptosis in thymocytes. J Immunol 176(7):4066-74 |
| abstractText | The EphA receptor tyrosine kinases interact with membrane-bound ligands of the ephrin-A subfamily. Interaction induces EphA receptor oligomerization, tyrosine phosphorylation, and, as a result, EphA receptor signaling. EphA receptors have been shown to regulate cell survival, migration, and cell-cell and cell-matrix interactions. However, their functions in lymphoid cells are only beginning to be described. We show in this study that functional EphA receptors are expressed by murine thymocytes, including CD4(+)CD8(+), CD4(+)CD8(-), and CD4(-)CD8(+) subpopulations. We demonstrate that activation of EphA receptors by the ephrin-A1 ligand inhibits the anti-CD3-induced apoptosis of CD4(+)CD8(+) double-positive thymocytes. Furthermore, ephrin-A1 costimulation suppresses up-regulation of both the IL-2R alpha-chain (CD25) and early activation Ag CD69 and can block IL-2 production by CD4(+) single-positive cells. In agreement, EphA receptor activation in thymocytes also inhibits TCR-induced activation of the Ras-MAPK pathway. Our findings suggest that EphA receptor activation is antithetical to TCR signaling in thymocytes, and that the level of engagement by ephrin-A proteins on thymic APCs regulates thymocyte selection. |
