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A genome-wide analysis identifies a notch-RBP-Jκ-IL-7Rα axis that controls IL-17-producing γδ T cell homeostasis in mice
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 194(1)
- Publication Year :
- 2014
-
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-7Rαhigh 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.
- Subjects :
- T cell
Receptors, Antigen, T-Cell, alpha-beta
T-Lymphocytes
Immunology
Regulator
Notch signaling pathway
Biology
Antibodies
Interferon-gamma
Mice
medicine
Basic Helix-Loop-Helix Transcription Factors
Immunology and Allergy
Animals
Homeostasis
HES1
Receptor, Notch1
Gene
Cell Proliferation
Homeodomain Proteins
Mice, Knockout
Receptors, Interleukin-7
Interleukin-7
Interleukin-17
Receptors, Antigen, T-Cell, gamma-delta
In vitro
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Immunoglobulin J Recombination Signal Sequence-Binding Protein
Transcription Factor HES-1
Interleukin 17
Genome-Wide Association Study
Signal Transduction
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 194
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....9d9cf1195014f0497001bf338ff1931d