Lack of conventional dendritic cells is compatible with normal development and T cell homeostasis, but causes myeloid proliferative syndrome.
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.
Birnberg
Tal
T
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Bar-On
Liat
L
Sapoznikov
Anita
A
Caton
Michele L
ML
Cervantes-Barragán
Luisa
L
Makia
Divine
D
Krauthgamer
Rita
R
Brenner
Ori
O
Ludewig
Burkhard
B
Brockschnieder
Damian
D
Riethmacher
Dieter
D
Reizis
Boris
B
Jung
Steffen
S
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
D008565:Membrane Proteins; C084881:flt3 ligand protein; D007371:Interferon-gamma