title: Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome.
abstract: Dendritic cells are critically involved in the promotion and regulation of T cell responses. Here, we report a mouse strain that lacks conventional CD11c(hi) dendritic cells (cDCs) because of constitutive cell-type specific expression of a suicide gene. As expected, cDC-less mice failed to mount effective T cell responses resulting in impaired viral clearance. In contrast, neither thymic negative selection nor T regulatory cell generation or T cell homeostasis were markedly affected. Unexpectedly, cDC-less mice developed a progressive myeloproliferative disorder characterized by prominent extramedullary hematopoiesis and increased serum amounts of the cytokine Flt3 ligand. Our data identify a critical role of cDCs in the control of steady-state hematopoiesis, revealing a feedback loop that links peripheral cDCs to myelogenesis through soluble growth factors, such as Flt3 ligand.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Birnberg
authors.forename: Liat
authors.initials: L
authors.lastname: Bar-On
authors.forename: Anita
authors.initials: A
authors.lastname: Sapoznikov
authors.forename: Michele L
authors.initials: ML
authors.lastname: Caton
authors.forename: Luisa
authors.initials: L
authors.lastname: Cervantes-Barragán
authors.forename: Divine
authors.initials: D
authors.lastname: Makia
authors.forename: Rita
authors.initials: R
authors.lastname: Krauthgamer
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.forename: Damian
authors.initials: D
authors.lastname: Brockschnieder
authors.forename: Dieter
authors.initials: D
authors.lastname: Riethmacher
authors.forename: Boris
authors.initials: B
authors.lastname: Reizis
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009196:Myeloproliferative Disorders / Q000276:immunology* / Q000378:metabolism; D013577:Syndrome; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein; D007371:Interferon-gamma