| RRC ID |
31871
|
| 著者 |
Nakamura M, Shibata K, Hatano S, Sato T, Ohkawa Y, Yamada H, Ikuta K, Yoshikai Y.
|
| タイトル |
A genome-wide analysis identifies a notch-RBP-Jκ-IL-7Rα axis that controls IL-17-producing γδ T cell homeostasis in mice.
|
| ジャーナル |
J Immunol
|
| Abstract |
Notch signaling is an important regulator for the development and function of both αβ and γδ 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(+)) γδ T cells. To gain insight into additional roles for the Notch axis in the homeostasis of γδ T cells, we performed a genome-wide analysis of Notch target genes and identified the novel promoter site of IL-7Rα driven by the Notch-RBP-Jκ pathway. Constitutive Notch signaling had the potential to induce IL-7Rα expression on γδ T cells in vivo, as well as in vitro, whereas conditional deletion of RBP-Jκ abrogated IL-7Rα expression, but not Hes1 expression, by γδ T cells and selectively reduced the pool size of IL-7Rα(high) IL-17(+) γδ T cells in the periphery. In the absence of IL-7Rα-mediated signaling, IL-17(+) γδ T cells were barely maintained in adult mice. Addition of exogenous IL-7 in vitro selectively expanded IL-17(+) γδ T cells. Thus, our results revealed a novel role for the Notch-RBP-Jκ-IL-7Rα axis that is independent of Hes1 for homeostasis of IL-17(+) γδ T cells.
|
| 巻・号 |
194(1)
|
| ページ |
243-51
|
| 公開日 |
2015-1-1
|
| DOI |
10.4049/jimmunol.1401619
|
| PII |
jimmunol.1401619
|
| PMID |
25429074
|
| MeSH |
Animals
Antibodies / immunology
Basic Helix-Loop-Helix Transcription Factors / biosynthesis
Cell Proliferation / drug effects
Genome-Wide Association Study
Homeodomain Proteins / biosynthesis
Homeostasis
Immunoglobulin J Recombination Signal Sequence-Binding Protein / genetics
Immunoglobulin J Recombination Signal Sequence-Binding Protein / immunology*
Interferon-gamma / biosynthesis
Interleukin-17 / biosynthesis*
Interleukin-7 / biosynthesis
Interleukin-7 / pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptor, Notch1 / immunology*
Receptors, Antigen, T-Cell, alpha-beta / immunology
Receptors, Antigen, T-Cell, gamma-delta / immunology*
Receptors, Interleukin-7 / biosynthesis
Receptors, Interleukin-7 / immunology*
Signal Transduction
T-Lymphocytes / immunology
Transcription Factor HES-1
|
| IF |
4.886
|
| 引用数 |
13
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC01071 |
