title: Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.
abstract: Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life.
authors: University of Basel Children's Hospital, 4056 Basel, Switzerland; Developmental Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland;
authors: Anne
authors: A
authors: Baerenwaldt
authors: University of Basel Children's Hospital, 4056 Basel, Switzerland; Developmental Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland;
authors: Nicole
authors: N
authors: von Burg
authors: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland; and.
authors: Matthias
authors: http://orcid.org/0000-0002-2748-7758
authors: M
authors: Kreuzaler
authors: Department of Infection Biology, University Clinic of Erlangen, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors: Selina
authors: S
authors: Sitte
authors: University of Basel Children's Hospital, 4056 Basel, Switzerland; Developmental Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland;
authors: Edit
authors: E
authors: Horvath
authors: University of Basel Children's Hospital, 4056 Basel, Switzerland; Developmental Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland;
authors: Annick
authors: A
authors: Peter
authors: Department of Infection Biology, University Clinic of Erlangen, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors: David
authors: D
authors: Voehringer
authors: Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland; and.
authors: Antonius G
authors: AG
authors: Rolink
authors: University of Basel Children's Hospital, 4056 Basel, Switzerland; Developmental Immunology, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland; daniela.finke@unibas.ch.
authors: Daniela
authors: D
authors: Finke
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D005333:Fetus; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology*; D007150:Immunohistochemistry; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000276:immunology*; D038041:Lymphopoiesis / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology*
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein