title: Critical role for miR-181a/b-1 in agonist selection of invariant natural killer T cells.
abstract: T-cell receptor (TCR) signal strength determines selection and lineage fate at the CD4(+)CD8(+) double-positive stage of intrathymic T-cell development. Members of the miR-181 family constitute the most abundantly expressed microRNA at this stage of T-cell development. Here we show that deletion of miR-181a/b-1 reduced the responsiveness of double-positive thymocytes to TCR signals and virtually abrogated early invariant natural killer T (iNKT) cell development, resulting in a dramatic reduction in iNKT cell numbers in thymus as well as in the periphery. Increased concentrations of agonist ligand rescued iNKT cell development in miR-181a/b-1(-/-) mice. Our results define a critical role of miR-181a/b-1 in early iNKT cell development and show that miR-181a/b-1 sets a TCR signaling threshold for agonist selection.
authors.affiliation: Institute for Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Ziętara
authors.forename: Marcin
authors.initials: M
authors.lastname: Łyszkiewicz
authors.forename: Katrin
authors.initials: K
authors.lastname: Witzlau
authors.forename: Ronald
authors.initials: R
authors.lastname: Naumann
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.forename: Jörg
authors.initials: J
authors.lastname: Langemeier
authors.forename: Jens
authors.initials: J
authors.lastname: Bohne
authors.forename: Inga
authors.initials: I
authors.lastname: Sandrock
authors.forename: Matthias
authors.initials: M
authors.lastname: Ballmaier
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.forename: Andreas
authors.initials: A
authors.lastname: Krueger
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D060966:Clonal Selection, Antigen-Mediated / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism
chemical_list: D008024:Ligands; D035683:MicroRNAs; D016693:Receptors, Antigen, T-Cell, alpha-beta; C529100:mirn181 microRNA, mouse