| First Author | Furukawa T | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 33692 | PubMed ID | 27659682 |
| Mgi Jnum | J:253768 | Mgi Id | MGI:6102543 |
| Doi | 10.1038/srep33692 | Citation | Furukawa T, et al. (2016) Transmission of survival signals through Delta-like 1 on activated CD4(+) T cells. Sci Rep 6:33692 |
| abstractText | Notch expressed on CD4(+) T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4(+) T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4(+) T cells from Dll1(-/-) and control mice into recipient mice followed by immunization revealed a rapid decline of CD4(+) T cells from Dll1(-/-) mice compared with control cells. Dll1(-/-) mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4(+) T cells from Dll1(-/-) mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4(+) T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch-signaling important for the survival of activated CD4(+) T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses. |
