title: Responsiveness of Developing T Cells to IL-7 Signals Is Sustained by miR-17∼92.
abstract: miRNAs regulate a large variety of developmental processes including development of the immune system. T cell development is tightly controlled through the interplay of transcriptional programs and cytokine-mediated signals. However, the role of individual miRNAs in this process remains largely elusive. In this study, we demonstrated that hematopoietic cell-specific loss of miR-17∼92, a cluster of six miRNAs implicated in B and T lineage leukemogenesis, resulted in profound defects in T cell development both at the level of prethymic T cell progenitors as well as intrathymically. We identified reduced surface expression of IL-7R and concomitant limited responsiveness to IL-7 signals as a common mechanism resulting in reduced cell survival of common lymphoid progenitors and thymocytes at the double-negative to double-positive transition. In conclusion, we identified miR-17∼92 as a critical modulator of multiple stages of T cell development.
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Malte
authors.initials: M
authors.lastname: Regelin
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Jonas
authors.initials: J
authors.lastname: Blume
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Jens
authors.initials: J
authors.lastname: Pommerencke
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Ramin
authors.initials: R
authors.lastname: Vakilzadeh
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Katrin
authors.initials: K
authors.lastname: Witzlau
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Marcin
authors.initials: M
authors.lastname: Łyszkiewicz
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Natalia
authors.initials: N
authors.lastname: Ziętara
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Namita
authors.initials: N
authors.lastname: Saran
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany; and Division of Hematology and Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115.
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany; Krueger.Andreas@mh-hannover.de.
authors.forename: Andreas
authors.identifier: http://orcid.org/0000-0001-7873-7334
authors.initials: A
authors.lastname: Krueger
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: C491673:Il17ra protein, mouse; D015851:Interleukin-7; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; D053722:Receptors, Interleukin-17; C576410:interleukin-7, mouse