title: Limited niche availability suppresses murine intrathymic dendritic-cell development from noncommitted progenitors.
abstract: The origins of dendritic cells (DCs) and other myeloid cells in the thymus have remained controversial. In this study, we assessed developmental relationships between thymic dendritic cells and thymocytes, employing retrovirus-based cellular barcoding and reporter mice, as well as intrathymic transfers coupled with DC depletion. We demonstrated that a subset of early T-lineage progenitors expressed CX3CR1, a bona fide marker for DC progenitors. However, intrathymic transfers into nonmanipulated mice, as well as retroviral barcoding, indicated that thymic dendritic cells and thymocytes were largely of distinct developmental origin. In contrast, intrathymic transfers after in vivo depletion of DCs resulted in intrathymic development of non-T-lineage cells. In conclusion, our data support a model in which the adoption of T-lineage fate by noncommitted progenitors at steady state is enforced by signals from the thymic microenvironment unless niches promoting alternative lineage fates become available.
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany;
authors.forename: Marcin
authors.initials: M
authors.lastname: Łyszkiewicz
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany;
authors.forename: Natalia
authors.initials: N
authors.lastname: Ziętara
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany;
authors.forename: Lisa
authors.initials: L
authors.lastname: Föhse
authors.affiliation: Dr von Haunersches Kinderspital, University Children's Hospital, Munich, Germany;
authors.forename: Jacek
authors.initials: J
authors.lastname: Puchałka
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany;
authors.forename: Jana
authors.initials: J
authors.lastname: Diestelhorst
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany;
authors.forename: Katrin
authors.initials: K
authors.lastname: Witzlau
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany;
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany; and Division of Hematology and Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany;
authors.forename: Andreas
authors.identifier: http://orcid.org/0000-0001-7873-7334
authors.initials: A
authors.lastname: Krueger
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D055153:Stem Cell Niche / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*