title: A genome-wide analysis identifies a notch-RBP-Jκ-IL-7Rα axis that controls IL-17-producing γδ T cell homeostasis in mice.
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.
authors.affiliation: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; k_shibata@bioreg.kyushu-u.ac.jp.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shibata
authors.affiliation: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Shinya
authors.initials: S
authors.lastname: Hatano
authors.affiliation: Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Epigenetics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; and.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Hisakata
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Yoshikai
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D055106:Genome-Wide Association Study; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006706:Homeostasis; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis*; D015851:Interleukin-7 / Q000096:biosynthesis / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051881:Receptor, Notch1 / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D000072056:Transcription Factor HES-1
chemical_list: D000906:Antibodies; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D007371:Interferon-gamma; D020381:Interleukin-17; D015851:Interleukin-7; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020395:Receptors, Interleukin-7; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C497762:Notch1 protein, mouse