| First Author | Nakamura M | Year | 2015 |
| Journal | J Immunol | Volume | 194 |
| Issue | 1 | Pages | 243-51 |
| PubMed ID | 25429074 | Mgi Jnum | J:230688 |
| Mgi Id | MGI:5763541 | Doi | 10.4049/jimmunol.1401619 |
| Citation | Nakamura M, et al. (2015) A genome-wide analysis identifies a notch-RBP-Jkappa-IL-7Ralpha axis that controls IL-17-producing gammadelta T cell homeostasis in mice. J Immunol 194(1):243-51 |
| abstractText | Notch signaling is an important regulator for the development and function of both alphabeta and gammadelta T cells, whereas roles of Notch signaling in T cell maintenance remain unclear. We reported previously that the Notch-Hes1 pathway was involved in the intrathymic development of naturally occurring IL-17-producing (IL-17(+)) gammadelta T cells. To gain insight into additional roles for the Notch axis in the homeostasis of gammadelta T cells, we performed a genome-wide analysis of Notch target genes and identified the novel promoter site of IL-7Ralpha driven by the Notch-RBP-Jkappa pathway. Constitutive Notch signaling had the potential to induce IL-7Ralpha expression on gammadelta T cells in vivo, as well as in vitro, whereas conditional deletion of RBP-Jkappa abrogated IL-7Ralpha expression, but not Hes1 expression, by gammadelta T cells and selectively reduced the pool size of IL-7Ralpha(high) IL-17(+) gammadelta T cells in the periphery. In the absence of IL-7Ralpha-mediated signaling, IL-17(+) gammadelta T cells were barely maintained in adult mice. Addition of exogenous IL-7 in vitro selectively expanded IL-17(+) gammadelta T cells. Thus, our results revealed a novel role for the Notch-RBP-Jkappa-IL-7Ralpha axis that is independent of Hes1 for homeostasis of IL-17(+) gammadelta T cells. |
