RRC ID 31871
Author Nakamura M, Shibata K, Hatano S, Sato T, Ohkawa Y, Yamada H, Ikuta K, Yoshikai Y.
Title A genome-wide analysis identifies a notch-RBP-Jκ-IL-7Rα axis that controls IL-17-producing γδ T cell homeostasis in mice.
Journal 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.
Volume 194(1)
Pages 243-51
Published 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 4.718
Times Cited 4
Mice Floxed RBP-J(RBRC01071)